Photodynamic therapy for actinic keratosis of the forehead and scalp with the Aktilite CL 128: Is there a cut-off value for PpIX-weighted irradiance for effective treatment?

BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is an established treatment for actinic keratosis (AK). Among the approved protocols in Europe, the most widely used involves irradiation with the Aktilite CL 128 (C-PDT). We aimed to assess the heterogeneity of irradiance over the treatment area when using C-PDT. We also investigated whether there is a cut-off value for protoporphyrin IX (PpIX)-weighted irradiance that may predict the treatment outcome of C-PDT. METHODS: An Ophir PD300 photodiode sensor connected to an Ophir Laser Star power meter was used to measure the irradiance delivered to 114 AKs of the scalp and forehead of 19 patients treated with C-PDT. The PpIX-weighted irradiances were deduced and cross-referenced with the complete responses at 3 months. RESULTS: From the measured irradiances ranging from 0.25 to 60 mW/cm2 (average: 31.94 mW/cm2 ), a standard deviation of 17.17 mW/cm2 was computed. Irradiance heterogeneity over the treatment area during C-PDT was demonstrated. The 66/114 AKs with a complete response at 3 months (57.89%) received a mean PpIX-weighted irradiance of 0.52 mW/cm2 vs 0.56 mW/cm2 for the resistant 48/114 AKs (42.11%). No significant effect of PpIX-weighted irradiance on the complete response at 3 months was found (odds ratio for a 0.1-unit change, 0.96; 95% confidence interval, 0.83 to 1.10; P = 0.53). Therefore, no cut-off value for PpIX-weighted irradiance that predicts treatment outcome could be identified. CONCLUSIONS: A device enabling homogeneous irradiation at a lower irradiance than the Aktilite CL 128 may therefore be suitable. This lower irradiance may further increase the treatment tolerance by patients.

Comparison of 10 efficient protocols for photodynamic therapy of actinic keratosis: How relevant are effective light dose and local damage in predicting the complete response rate at 3 months?

BACKGROUND: Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient. OBJECTIVES: This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage. METHODS: The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment. RESULTS: The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found. CONCLUSIONS: Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. 50:576-589, 2018. © 2018 Wiley Periodicals, Inc.

Treatment of a vulvar Paget's disease by photodynamic therapy with a new light emitting fabric based device.

INTRODUCTION: The non-invasive vulvar Paget's disease is an intra-epidermal carcinoma with glandular characteristics. It appears like an erythematous plaque. The main symptoms are pruritus and pain. The standard treatment is surgical excision in depth. This treatment is complicated with a severe morbidity and photodynamic therapy can be an alternative choice. However, the pain experienced during the photodynamic treatment of vulvar lesion is intense and leads to a premature interruption of the treatment. The light emitting fabric is a part of a device under clinical evaluation for the treatment of actinic keratosis with photodynamic therapy. We report the observation of a vulvar Paget's disease treated by this device with a satisfactory result and an excellent tolerance. CLINICAL OBSERVATION: The patient has been diagnosed with non-invasive vulvar Paget's disease for 25 years. The disease recurred constantly despite several imiquimod applications, LASER treatments and conventional photodynamic therapy. These procedures were complicated with intense pain. To improve the tolerance, we performed three PDT sessions a month apart using a 16% methyl-aminolevulinate cream (Metvixia® Galderma, Lausanne, Switzerland) with the light emitting fabric at low irradiance (irradiance = 6 mW/cm2 -fluence = 37 J/cm2 ) with a satisfactory result and an excellent tolerance. DISCUSSION: There are no controlled trials evaluating the efficacy of photodynamic therapy in the treatment of vulvar Paget's disease. The treatment and follow-up protocols in the literature are heterogeneous. Pain is the most common side effect with greater intensity for perineal locations where photodynamic therapy is impractical outside of anesthesia or hypnosis. CONCLUSION: We report the case of a multirecidivant non-invasive vulvar Paget's disease treated with a satisfactory result and an excellent tolerance by the new light emitting fabric device. A specific study is required but the light emitting fabric could be indicated for the treatment of Paget disease of perineal location. Lasers Surg. Med. 49:177-180, 2017. © 2017 Wiley Periodicals, Inc.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

OBJECTIVE AND STUDY DESIGN: Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. METHODS: This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. RESULTS: The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. CONCLUSION: This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc.

Evaluating the Noninferiority of a New Photodynamic Therapy (Flexitheralight) Compared With Conventional Treatment for Actinic Keratosis: Protocol for a Phase 2 Study.

BACKGROUND: Actinic keratosis (AK) is characterized by preinvasive, cancerous lesions on sun-exposed skin that negatively affect patient quality of life and may progress to invasive squamous cell carcinoma (SCC). If untreated, AK may either regress or progress to SCC, with significant morbidity and possible lethal outcomes. The most commonly used treatments for AK are cryotherapy, topical chemotherapy and, more recently, photodynamic therapy (PDT). This clinical study is part of a project that aims to create specific light-emitting fabrics (LEFs) that strongly improve the efficiency and reliability of PDT as a treatment for AK. OBJECTIVE: This study aims to compare the efficacy and tolerability of a new PDT protocol involving the Flexitheralight device (N-PDT) with the classical protocol involving the Aktilite CL 128 device (C-PDT; Galderma Laboratories) for the treatment of AK. All participants receive both protocols. The primary objective of this study is to compare the lesion response rate after 3 months of N-PDT with C-PDT. Secondary objectives are evaluations of pain and local tolerance during treatment, clinical evolution of the subject's skin, and evaluations of patient quality of life and satisfaction. METHODS: The study is a split-face, intraindividual comparison of two PDT protocols. The total number of patients recruited was 42. Patients were exposed to a continuous red light with the Aktilite CL 128 device on one side of the face and to fractionated red illumination with the new device, Flexitheralight, on the other side of the face. Males or females over the age of 18 years with a clinical diagnosis of at least 10 previously untreated, nonpigmented, nonhyperkeratotic grade I and II AK lesions of the forehead and/or scalp were included and were recruited from the Department of Dermatology of the Centre Hospitalier Universitaire de Lille. The patients came to the investigational center for one treatment session (day 1), and they were followed up after 7 days, 3 months and 6 months. A second treatment session was performed on day 111 in cases in which an incomplete response was observed at the 3-month follow-up. Data will be analyzed using SAS software version 9.4 (SAS Institute Inc). Continuous variables will be reported as means and standard deviations, and categorical variables will be reported as frequencies and percentages. The Shapiro-Wilk test will be used to assess the normality of the distribution. RESULTS: The clinical investigation was performed by July 2018. Data analysis was performed at the end of 2018, and results are expected to be published in early 2019. CONCLUSIONS: This phase II clinical trial aims to evaluate the noninferior efficacy and superior tolerability of N-PDT compared to that of C-PDT. If N-PDT is both efficacious and tolerable, N-PDT could become the treatment of choice for AK due to its ease of implementation in hospitals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03076918; https://clinicaltrials.gov/ct2/show/NCT03076918 (archived by WebCite at http://www.webcitation.org/771KA0SSK). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11530.

Can daylight-PDT be performed indoor?

Natural DayLight-mediated PhotoDynamic Therapy (NDL-PDT) is an efficacious treatment option for thin actinic keratosis that offers advantages over conventional PDT in terms of tolerability and cost. It is now accepted that the minimum criteria required for effective NDL-PDT is a dose of 4 J/cm² with a treatment time of 2 hours and a minimum temperature of 10 °C, corresponding to a minimum illuminance of 11,000 lux. This value is easily achievable: 20,000 lux can be obtained during a typical overcast day at midday. It can reach 110,000 lux with a bright sunlight. However, it is limited to certain times of the year at our latitude. However rain and cold temperatures appear the main limitations of NDL-PDT. Greenhouses make possible to perform the illumination even in harsh weather conditions. Furthermore, it is difficult to install a greenhouse everywhere. Several solutions are now proposed to carry out indoor illumination so-called artificial white light or simulated daylight (SDL-PDT). Illumination sources installed at the ceiling of the treatment room is one option. Several lamp pairs can be combined to illuminate groups of patients simultaneously. A surgical theatre light can be used or dedicated systems using white LEDs can be used to deliver the required illumination dose. In conclusion, Indoor lightning (or simulated daylight: SDL-PDT or Artificial White Light: AWL) could offer an interesting alternative to NDL-PDT.

Photodynamic therapy for actinic keratosis: Is the European consensus protocol for daylight PDT superior to conventional protocol for Aktilite CL 128 PDT?

BACKGROUND: Topical photodynamic therapy (PDT) is an established treatment modality for various dermato-oncologic conditions. In Europe, initially requiring irradiation with red light, PDT of actinic keratosis (AK) can now also be carried out with exposure to daylight that has been clinically proven to be as effective as and less painful than red light. OBJECTIVES: In this paper, we propose a comparison between the conventional protocol for Aktilite CL 128 (red light source) PDT and the European consensus protocol for daylight PDT - with the exposure is assumed to be performed during either a clear sunny day or an overcast day - in the treatment of AK with methyl aminolevulinate through a mathematical modeling. METHOD: This already published modeling that is based on an iterative procedure alternating determination of the local fluence rate and updating of the local optical properties enables to estimate the local damage induced by the therapy. RESULTS: The European consensus protocol for daylight PDT during a sunny day and an overcast day provides, on average, 6.50 and 1.79 times higher PDT local damages at the end of the treatment than those obtained using the conventional protocol for Aktilite CL 128 PDT, respectively. CONCLUSIONS: Results analysis shows that, even performed during an overcast day, the European consensus protocol for daylight PDT leads to higher PDT local damages than the efficient conventional protocol for Aktilite CL 128.