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

International audienceBackground: 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 2 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

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?

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Low-irradiance red light compared to conventional red light in photodynamic therapy of actinic keratosis: a way to reduce pain during treatment

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COMPARISON OF THREE LIGHT DOSES IN THE PHOTODYNAMIC TREATMENT OF ACTINIC KERATOSIS USING MATHEMATICAL MODELING

International audienceAbstract. Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm², 75 mW/cm², 500 s; blue light dose, 10 J/cm², 10 mW/cm², 1000 s; and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable

Photodynamic therapy for actinic keratosis: a trend towards a decrease in irradiance without loss of efficacy for a better tolerability

International audiencePhotodynamic therapy (PDT) is an established treatment for actinic keratosis (AK). The conventional approved PDT protocol in Europe (C-PDT) involves red-light photoactivation at irradiances higher than 60 mW/cm 2 , making the treatment painful. Several clinical studies have reported similar efficacy and better tolerability when using red-light photoactivation at lower irradiances. The aim of the study was to investigate whether there is a minimum irradiance threshold for red-light photoactivation above which there is no further improvement in efficacy. A photodiode sensor connected to a power meter was used to measure the irradiance delivered to 114 AKs on the scalp and forehead of 19 patients during C-PDT using the Aktilite CL 128 (Galderma SA, Switzerland). The widely ranging measured irradiances, resulting from the heterogeneous photoactivation over the treatment area provided by the Aktilite CL 128, were cross-referenced with the clinically evaluated complete responses (CR) at 3 months. The 66 AKs in CR at 3 months received an average irradiance of 30.9 mW/cm 2 (standard deviation: 16.7 mW/cm 2) compared to 33.3 mW/cm 2 (standard deviation: 17.9 mW/cm 2) for the 48 AKs in incomplete response. No significant effect of the irradiance on the CR at 3 months was found (odds ratio for a 6 mW/cm 2-unit change, 0.96; 95% confidence interval, 0.83 to 1.10; p=0.53). No minimum irradiance threshold could therefore be determined in the considered irradiance range. A red-light device enabling homogeneous irradiation at a lower irradiance than the Aktilite CL 128 may therefore provide similar efficacy and higher treatment tolerability than C-PDT

Real-time light dosimetry for intra-cavity photodynamic therapy: Application for pleural mesothelioma treatment

International audienceComplete and homogeneous illumination of the target is necessary for the success of a photodynamic therapy (PDT) procedure. In most applications, light dosimetry is done using detectors placed at strategic locations of the target. In this study we propose a novel approach based on the combination of light distribution modeling with spatial localization of the light applicator for real time estimation and display of the applied dose on medical images. The feasibility approach is demonstrated for intrapleural PDT of malignant pleural mesothelioma

Interstitial Photodynamic Therapy for Glioblastomas: A Standardized Procedure for Clinical Use

Glioblastomas (GBMs) are high-grade malignancies with a poor prognosis. The current standard of care for GBM is maximal surgical resection followed by radiotherapy and chemotherapy. Despite all these treatments, the overall survival is still limited, with a median of 15 months. For patients harboring inoperable GBM, due to the anatomical location of the tumor or poor general condition of the patient, the life expectancy is even worse. The challenge of managing GBM is therefore to improve the local control especially for non-surgical patients. Interstitial photodynamic therapy (iPDT) is a minimally invasive treatment relying on the interaction of light, a photosensitizer and oxygen. In the case of brain tumors, iPDT consists of introducing one or several optical fibers in the tumor area, without large craniotomy, to illuminate the photosensitized tumor cells. It induces necrosis and/or apoptosis of the tumor cells, and it can destruct the tumor vasculature and produces an acute inflammatory response that attracts leukocytes. Interstitial PDT has already been applied in the treatment of brain tumors with very promising results. However, no standardized procedure has emerged from previous studies. Herein, we propose a standardized and reproducible workflow for the clinical application of iPDT to GBM. This workflow, which involves intraoperative imaging, a dedicated treatment planning system (TPS) and robotic assistance for the implantation of stereotactic optical fibers, represents a key step in the deployment of iPDT for the treatment of GBM. This end-to-end procedure has been validated on a phantom in real operating room conditions. The thorough description of a fully integrated iPDT workflow is an essential step forward to a clinical trial to evaluate iPDT in the treatment of GBM

A Warp-Knitted Light-Emitting Fabric-Based Device for In Vitro Photodynamic Therapy: Description, Characterization, and Application on Human Cancer Cell Lines

Photodynamic therapy (PDT) appears to be a promising strategy in biomedical applications. However, the complexity of its parameters prevents wide acceptance. This work presents and characterizes a novel optical device based on knitted light-emitting fabrics and dedicated to in vitro PDT involving low irradiance over a long illumination period. Technical characterization of this device, called CELL-LEF, is performed. A cytotoxic study of 5-ALA-mediated PDT on human cancer cell lines is provided as a proof of concept. The target of delivering an irradiance of 1 mW/cm2 over 750 cm2 is achieved (mean: 0.99 mW/cm2; standard deviation: 0.13 mW/cm2). The device can maintain a stable temperature with the mean thermal distribution of 35.1 °C (min: 30.7 °C; max: 38.4 °C). In vitro outcomes show that 5-ALA PDT using CELL-LEF consistently and effectively induced a decrease in tumor cell viability: Almost all the HepG2 cells died after 80 min of illumination, while less than 60% of U87 cell viability remained. CELL-LEF is suitable for in vitro PDT involving low irradiance over a long illumination period

A New Light-Emitting, Fabric-Based Device for Photodynamic Therapy of Actinic Keratosis: Protocol for a Randomized, Controlled, Multicenter, Intra-Individual, Phase II Noninferiority Study (The Phosistos Study)

International audienceBackground: Actinic keratosis (AK) is a common early in situ skin carcinoma caused by long-term sun exposure and usually develops on sun-exposed skin areas. Left untreated, AK may progress to squamous cell carcinoma. To prevent such risk, most clinicians routinely treat AK. Therapy options for AK include cryotherapy, topical treatments, curettage, excision surgery, and photodynamic therapy (PDT).Objective: The aim of this study is to assess the noninferiority, in terms of efficacy at 3 months, of a PDT protocol involving a new light-emitting device (PDT using the Phosistos protocol [P-PDT]) compared with the conventional protocol (PDT using the conventional protocol [C-PDT]) in the treatment of AK.Methods: In this randomized, controlled, multicenter, intra-individual, phase II noninferiority clinical study, subjects with AK of the forehead and scalp are treated with P-PDT on one area and with C-PDT on the contralateral area. In both areas, lesions are prepared and methyl aminolevulinate (MAL) is applied. Thirty minutes after MAL application, the P-PDT area is exposed to red light at low irradiance (1.3 mW/cm2) for 2.5 hours so that a light dose of 12 J/cm2 is achieved. In the control area (C-PDT area), a 37 J/cm2 red light irradiation is performed 3 hours after MAL application. Recurrent AK at 3 months is retreated. The primary end point is the lesion complete response rate at 3 months. Secondary end points include pain scores at 1 day, local tolerance at 7 days, lesion complete response rate at 6 months, cosmetic outcome at 3 and 6 months, and patient-reported quality of life and satisfaction throughout the study. A total of 45 patients needs to be recruited.Results: Clinical investigations are complete: 46 patients were treated with P-PDT on one area (n=285 AK) and with C-PDT on the contralateral area (n=285 AK). Data analysis is ongoing, and statistical results will be available in the first half of 2019.Conclusions: In case of noninferiority in efficacy and superiority in tolerability of P-PDT compared with C-PDT, P-PDT could become the treatment of choice for AK.Trial registration: ClinicalTrials.gov NCT03076892; https://clinicaltrials.gov/ct2/show/NCT03076892 (Archived by WebCite at http://www.webcitation.org/779qqVKek).International registered report identifier (irrid): DERR1-10.2196/12990