Daylight-mediated Photodynamic Therapy Research Articles

Daylight-Mediated Photodynamic Therapy for Actinic Keratosis

ABSTRACT Actinic (solar) keratoses are premalignant lesions caused by prolonged exposure to ultraviolet radiation, with the potential to progress into squamous cell carcinoma. Hence, use of appropriate therapies is critical for effective treatment. Daylight-mediated photodynamic therapy with methyl aminolevulinate cream is a convenient new option for the safe and effective treatment of actinic (solar) keratosis lesions, offering similar efficacy to conventional photodynamic therapy, nearly painless treatment, and reduced in-clinic times. Use of appropriate therapies and optimization of clinical practice are critical for safe and effective treatment. Nurses play a key role in ensuring best clinical practice and effective treatment. This article explains the practicalities and principles of daylight-mediated photodynamic therapy to ensure best practice by treating nurses.

Daylight Photodynamic Therapy for Actinic Keratoses.

Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, but with minimal therapy-associated pain. Comparison with conventional PDT indicates similar efficacy for thin and moderate-thickness AKs, but with significantly less discomfort/pain, driving a patient preference for daylight-mediated PDT (DL-PDT) compared with conventional PDT using high-intensity office/hospital-based light sources. Treatment protocol involves the application of a photosensitizing agent without occlusion and subsequent exposure to ambient daylight within 30min, with patients exposed to daylight for 1.5-2.0h. Pivotal randomized controlled trials in Europe and Australia have confirmed the efficacy of methyl aminolevulinic acid (MAL) DL-PDT in comparison with conventional MAL-PDT for mild and moderate-thickness lesions on the face and scalp. Initial clearance rates of 70-89% are reported. DL-PDT using a nanoemulsion aminolevulinic acid (ALA) has recently been shown to be at least as effective as MAL DL-PDT in treating mild and moderate-thickness AKs. DL-PDT may offer a better-tolerated method for treating patients with extensive AK disease. There is emerging literature on the potential for field PDT to reduce the number of new AKs developing, potentially preventing/slowing skin cancer development. Conventional PDT remains established as a therapy for Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas (BCCs), and AKs. The evidence for the use of DL-PDT beyond AK is limited, although has been reported in actinic cheilitis, superficial BCC, and acne and cutaneous leishmaniasis. There is emerging interest in combination therapy for AK, using one or more field therapies such as DL-PDT as an option to complement with localized treatment for residual lesions. We review current recommendations and consider the appropriate place for DL-PDT in our treatment armamentarium.

Daylight-Mediated Photodynamic Therapy With Methyl Aminolevulinate in Actinic Keratosis Treatment.

Research has shown daylight-mediated photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) to be effective, tolerable, and convenient, with excellent patient satisfaction and cosmesis. Although success has been demonstrated in areas with similar latitudes to Switzerland and Scandinavia, this treatment has not been studied in a Canadian population. The purpose of this study is to investigate the effectiveness, safety, and patient satisfaction of daylight-mediated methyl 5-aminolevulinate (MAL)-PDT to make recommendations for its use in Canadian practice. A retrospective chart review of patients who received treatment of daylight-mediated MAL-PDT for the indication of AK at the Institute of Cosmetic and Laser Surgery in Oakville, Ontario, between 2009 and 2016. A total of 112 patients were included, consisting of 94 males and 18 females with a mean age of 63.79 years. A total of 177 sites were treated among all patients, mostly consisting of the face (n = 92) and scalp (n = 55). A total of 13.4% of patients experienced side effects, the most common being redness (n = 4) and scabbing (n = 4). Of the 42 patients who expressed their level of satisfaction, 83.3% reported being happy with the treatment, χ2(1) = 18.67, P ≤ .05; 6.3% of patients were noted to be completely clear, 86.6% had a good response, 0.9% had a mild response, and 0% had no response, χ2(1) = 101.04, P ≤ .05. Daylight-mediated MAL-PDT is a suitable treatment option for AK lesions in a Canadian population due to the demonstrated efficacy, patient satisfaction, tolerability, and convenience.

Daylight Photodynamic Therapy Versus 5-Fluorouracil for the Treatment of Actinic Keratosis: A Case Series.

IntroductionThe incidence of actinic keratosis (AK) continues to increase worldwide. Currently available options for the treatment of AK include topical 5-fluorouracil (5-FU) and daylight-mediated photodynamic therapy (DL-PDT). This split-face pilot study compared DL-PDT using 16% methyl aminolevulinate (MAL) cream versus 5-FU cream in patients with AK on the face/scalp.MethodsFive male subjects (mean age 70 years) with grade I–III AK on the face/scalp were enrolled. Subjects received a single session of DL-PDT with 16% MAL on one side and topical 5% 5-FU for 21 days on the other side. Evaluations of efficacy, safety, and subject satisfaction were conducted 48 h, 7 days, 14 days, 1 month, and 3 months after treatment.ResultsAt 3 months, the lesion complete response rate was 80% and 93% for DL-PDT and 5-FU, respectively. Lesion partial response was 20% and 7%, respectively. Fewer treatment-related adverse events (AEs) were reported with DL-PDT than with 5-FU, and they resolved spontaneously in 5–7 and 27–30 days, respectively. Subjects preferred DL-PDT because of the lower incidence of AEs and rapid recovery compared with 5-FU.ConclusionDL-PDT is a convenient alternative to 5-FU with good efficacy and a favorable safety profile, allowing patients to effectively treat their AK without compromising their social life.FundingGalderma.

Pretreatment with 5-Fluorouracil Cream Enhances the Efficacy of Daylight-mediated Photodynamic Therapy for Actinic Keratosis

The efficacy of photodynamic therapy (PDT) with methyl aminolevulinate is reduced when treating actinic keratosis (AK) on the extremities in comparison with the face and scalp. Studies indicate that PDT efficacy can be improved by combining PDT with other treatment modalities. This randomized intra-individual study investigated whether pretreatment with topical 5% 5-fluorouracil (5-FU) enhanced the treatment efficacy of daylight-mediated PDT in 24 patients with AKs on the hands. One hand of each patient was given 7 days of pretreatment with 5-FU twice daily before daylight-PDT, whereas the other hand was treated with daylight-PDT alone. At 3-month follow-up the overall lesion response rate was significantly higher for the combination of 5-FU and daylight-PDT (62.7%) than for daylight-PDT alone (51.8%) (p = 0.001). Furthermore, pain and erythema in relation to treatment were similar in the 2 groups (p = 1.0 and p = 0.2, respectively). Combination therapy is a safe and effective method to improve daylight-PDT for acral AKs.

Daylight-Mediated Photodynamic Therapy for Actinic Keratosis

ABSTRACT Actinic (solar) keratoses are premalignant lesions caused by prolonged exposure to ultraviolet radiation, with the potential to progress into squamous cell carcinoma. Hence, use of appropriate therapies is critical for effective treatment. Daylight-mediated photodynamic therapy with methyl aminolevulinate cream is a convenient new option for the safe and effective treatment of actinic (solar) keratosis lesions, offering similar efficacy to conventional photodynamic therapy, nearly painless treatment, and reduced in-clinic times. Use of appropriate therapies and optimization of clinical practice are critical for safe and effective treatment. Nurses play a key role in ensuring best clinical practice and effective treatment. This article explains the practicalities and principles of daylight-mediated photodynamic therapy to ensure best practice by treating nurses.

Daylight-Mediated Photodynamic Therapy for Actinic Keratosis: Best Practice Guidelines

Daylight-Mediated Photodynamic Therapy for Actinic Keratosis: Best Practice Guidelines

Feasibility of daylight-mediated photodynamic therapy for actinic keratosis throughout the year in Central and South America: a meteorological study.

Daylight-mediated photodynamic therapy (DL-PDT) is an efficacious treatment option for thin actinic keratosis (AK) that offers advantages over conventional PDT in terms of tolerability, treatment duration, and cost. A clinical study conducted in Australia determined the mean irradiance during a 2-hour exposure to be 305.8 W/m(2) (range: 40-585 W/m(2) ). The protoporphyrin IX light dose is influenced by latitude, weather conditions, and time of year. A recent study of meteorological data concluded that DL-PDT can be performed effectively throughout the year in Australia. Based on the same hypothesis and applying the same methodology, the present study investigated the suitability of daylight to perform DL-PDT in Central and South America. Solar radiation and weather data were gathered and analyzed to assess daylight irradiance (light intensity) throughout a full year across 32 geographical locations in Central and South America. The minimum average daily solar irradiance reported was above 305.8 W/m(2) in all locations investigated throughout the year. Annual averages of daily irradiance ranged from 578 W/m(2) in Chihuahua, Mexico, to 321 W/m(2) in Puerto Montt, Chile. Daylight-mediated PDT for AK can be performed effectively throughout the year in Central and South America given that weather conditions permit a comfortable 2-hour direct exposure to daylight.

Alternatives to Outdoor Daylight Illumination for Photodynamic Therapy--Use of Greenhouses and Artificial Light Sources.

Daylight-mediated photodynamic therapy (daylight PDT) is a simple and pain free treatment of actinic keratoses. Weather conditions may not always allow daylight PDT outdoors. We compared the spectrum of five different lamp candidates for indoor “daylight PDT” and investigated their ability to photobleach protoporphyrin IX (PpIX). Furthermore, we measured the amount of PpIX activating daylight available in a glass greenhouse, which can be an alternative when it is uncomfortable for patients to be outdoors. The lamps investigated were: halogen lamps (overhead and slide projector), white light-emitting diode (LED) lamp, red LED panel and lamps used for conventional PDT. Four of the five light sources were able to photobleach PpIX completely. For halogen light and the red LED lamp, 5000 lux could photobleach PpIX whereas 12,000 lux were needed for the white LED lamp. Furthermore, the greenhouse was suitable for daylight PDT since the effect of solar light is lowered only by 25%. In conclusion, we found four of the five light sources and the greenhouse usable for indoor daylight PDT. The greenhouse is beneficial when the weather outside is rainy or windy. Only insignificant ultraviolet B radiation (UVB) radiation passes through the greenhouse glass, so sun protection is not needed.

Treatment of face and scalp solar (actinic) keratosis with daylight-mediated photodynamic therapy is possible throughout the year in Australia: Evidence from a clinical and meteorological study.

Background/ObjectivesSolar (actinic) keratosis (AK) is an emergent concern worldwide and is associated with an increased risk of development of non‐melanoma skin cancer, especially squamous cell carcinoma. Daylight‐mediated photodynamic therapy (DL‐PDT) using methyl aminolaevulinate cream has proved to be an effective, nearly painless, and more convenient alternative to conventional PDT for the treatment of AK. In a phase III, randomised, controlled trial performed in Australia, the mean irradiance (light intensity) received by patients during DL‐PDT treatment, assessed via a spectroradiometer, was 305 W/m2 (min. 40 to max. 585 W/m2) with similar efficacy irrespective of intensity or dose. The objective of the present meteorological study was to assess the suitability of natural daylight to perform DL‐PDT for the treatment of face and scalp AK during different periods of the year and different geographical locations and latitudes across Australia.MethodsTo determine daylight irradiance during a complete year in eight different geographical locations throughout Australia, we used meteorological software (Meteonorm, Meteotest, Bern, Switzerland), and available solar radiation and weather data from 1986–2005.ResultsThe average daily irradiance remained within the levels (40–585 W/m2) measured during the clinical DL‐PDT study in Australia, throughout the year and in all geographical locations investigated (yearly average from Darwin 548 W/m2 to Hobart 366 W/m2).Conclusions DL‐PDT for the treatment of face and scalp AK in Australia can be performed effectively throughout the entire year as long as weather conditions permit daylight exposure and allow participants to remain under direct light for 2 h.

Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus.

Daylight-mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe. To establish consensus recommendations for the use of daylight photodynamic therapy (DL-PDT) using topical methyl aminolaevulinate (MAL) in European patients with AKs. The DL-PDT consensus recommendations were developed on behalf of the European Society for Photodynamic Therapy in Dermatology and comprised of 10 dermatologists from different European countries with experience in how to treat AK patients with PDT. Consensus was developed based on literature review and experience of the experts in the treatment of AK using DL-PDT. The recommendations arising from this panel of experts provide general guidance on the use of DL-PDT as a dermatological procedure with specific guidance regarding patient selection, therapeutic indications, when to treat, pre-treatment skin preparation, MAL application and daylight exposure for patients with AK in different countries of Europe. This consensus recommendation provides a framework for physicians to perform DL-PDT with MAL cream while ensuring efficiency and safety in the treatment of patients with AK in different European countries.

Daylight-Mediated Photodynamic Therapy in Spain: Advantages and Disadvantages

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients.

Terapia fotodinámica con luz de día en España: ventajas y limitaciones

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated patients.

Artificial daylight photodynamic therapy with “non-inflammatory” doses of hexyl aminolevulinate only marginally delays SCC development in UV-exposed hairless mice

Photodynamic therapy (PDT) is effective for actinic keratoses, but is associated with pain and post-treatment inflammation. Daylight-mediated PDT and PpIX-precursors at low concentrations reduce pain and inflammation intensity. The objective was to evaluate the effect of repeated low-concentration PDT combined with artificial daylight on SCC development. Mice (n = 265) were exposed to simulated solar UV-irradiation (UVR) 3 times weekly mimicking "summer-dose"-exposure (3 SED). Selected groups of mice received a "winter-dose"-exposure (0.6 SED) for the first 90 days. PDT was delivered with 0.1%, 0.05% and 0.02% hexyl aminolevulinate (HAL) cream and artificial daylight for 2.5 hours (6 J cm(-2)) in different treatment regimes (1-3 times weekly, 45-days intervals, days 1-180 and from day 180 onwards). The primary end-point was the time to first SCC (1 mm diameter). 0.1% HAL-PDT given 3 times weekly slightly delayed SCC development and induced minimal inflammation. In winter- and summer UVR-treatment regimes, 0.1% HAL PDT delayed the time to first SCC compared to control UVR and placebo-PDT when mice were PDT-treated on days 1-180 (median 213 vs. 199 days, p = 0.011) and from day 180 onwards (median 218 vs. 199 days, p = 0.006). PDT with 0.05% and 0.02% HAL did not influence SCC development (medians 206 days, p = ns). In summer UVR-exposed mice, 0.1% HAL-PDT marginally postponed the time to first SCC compared to control UVR (median 160 days) when treatments were given 3 times weekly for 180 days (median 166, p = 0.01), but not for 90 days (median 161, p = 0.112). In conclusion, repeated low-concentration HAL-PDT combined with artificial daylight is well-tolerated, but only marginally delays SCC development in mice.

Neue Entwicklungen in der photodynamischen Therapie

We review new developments in recent years in photodynamic therapy. Since 2009 two new photosensitizers, a self-adhesive 5-aminolevulinic acid (ALA) patch and a nanoemulsion formulation of 5-aminolevulinic acid have been approved for the treatment of actinic keratoses. Pretreatment with ablative fractional lasers enhances penetration of the photosensitizer and enables intensified PDT in acral lesions and in field-cancerized skin. Several clinical trials have demonstrated the skin-rejuvenating effects of photodynamic therapy, while the underlying mechanisms of action have been clarified. The efficacy of photodynamic therapy has been shown in the treatment and prophylaxis of actinic keratoses in organ transplant recipients at high risk for developing skin cancer. We also summarize the results of available studies on daylight-mediated photodynamic therapy.

Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX-weighted daylight doses measured in six geographical locations

Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries. To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries. To calculate where and when daylight-PDT of AKs was possible in six different geographical locations using ground stations measuring PpIX-weighted daylight doses. PpIX-weighted daylight doses were measured using a dosimeter with a customer-specific photodiode with a detector sensitivity that mimics the PpIX absorption spectrum and measures in 'PpIX doses'. The dosimeters were built into ground stations that were placed in six geographical locations measuring from July to December 2008. Temperature data for each location were obtained from the internet. The maximal ultraviolet (UV) index for Copenhagen was obtained for the measuring period of the dosimeters. If the PpIX light dose should be above 8Jcm(-2) and the maximum temperature of the day at least 10°C, it was possible to treat patients on nearly all days until the middle of September in Reykjavik and Oslo, until the last week of October in Copenhagen and Regensburg, until the middle of November in Turin and all year in Israel. Where and when to perform daylight-PDT depends on the PpIX light dose and outdoor temperature. The PpIX light dose was influenced by the geographical location (latitude), weather condition and time of year. The UV index was not more suitable than temperature and weather to predict if the intensity of daylight would be sufficient for daylight-PDT.

Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study

Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P < 0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm(-2). Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.

A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp

A randomized, multicentre study of directed daylight exposure times of 1½ vs. 2½h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp

Daylight photodynamic therapy for actinic keratosis: an international consensus

Photodynamic therapy (PDT) is an attractive therapy for non-melanoma skin cancers including actinic keratoses (AKs) because it allows treatment of large areas; it has a high response rate and results in an excellent cosmesis. However, conventional PDT for AKs is associated with inconveniently long clinic visits and discomfort during therapy. In this article, we critically review daylight-mediated PDT, which is a simpler and more tolerable treatment procedure for PDT. We review the effective light dose, efficacy and safety, the need for prior application of sunscreen, and potential clinical scope of daylight-PDT. Three randomized controlled studies have shown that daylight-mediated PDT is an effective treatment of thin AKs. Daylight-mediated PDT is nearly pain-free and more convenient for both the clinics and patients. Daylight-mediated PDT is especially suited for patients with large field-cancerized areas, which can easily be exposed to daylight. Further investigations are necessary to determine at which time of the year and in which weather conditions daylight-mediated PDT will be possible in different geographical locations.

Continuous ultra‐low‐intensity artificial daylight is not as effective as red LED light in photodynamic therapy of multiple actinic keratoses

Daylight-mediated photodynamic therapy (PDT) is a simple and tolerable treatment of nonmelanoma skin cancer. It is of interest which light intensity is sufficient to prevent accumulation of protoporphyrin IX (PpIX) and effectively treat actinic keratoses (AKs). We compared the efficacy of PDT with light-emitting diode (LED) to daylight-mediated PDT with very low-intensity artificial daylight ('daylight') in the treatment of multiple AKs in the face or scalp. Twenty patients were treated with conventional methyl aminolevulinate (MAL) PDT in one area. Another area was, after half an hour of occlusive treatment with MAL, illuminated for 2.5 h with low-intensity 'daylight' (0.5 mW/cm(2) -3.7 mW/cm(2)) that corresponds to midday outdoor intensity in the Scandinavian winter. After 3 months, with a response rate of 52%, low-dose artificial daylight was less effective than conventional LED-PDT (63%) (P = 0.0017). The mean PpIX light dose during 'daylight' exposure was 2.23 J/cm(2) and the lower the PpIX light intensity, the higher the accumulation of PpIX (P = 0.003). Even very low-intensity/dose artificial daylight-mediated PDT of multiple AKs resulted in a response rate of more than 50%. However, to ensure efficacies equivalent to conventional LED-PDT, the treatment should not be conducted on very overcast days.