A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination

Kaw, Urvashi; Ilyas, Muneeb; Bullock, Taylor; Rittwage, Lisa; Riha, Margo; Vidimos, Allison; Hu, Bo; Warren, Christine; Maytin, Edward V.

doi:10.1016/j.jaad.2019.09.010

Cited by 38 publications

(38 citation statements)

References 20 publications

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“…To investigate mechanisms that might be responsible for similar rates of AK lesion clearance previously observed after conventional or painless PDT in humans (37), we designed experiments to simulate the two PDT regimens and performed a detailed time course analyses of underlying events in a murine AK model.…”

Section: Resultsmentioning

confidence: 99%

“…Less pain is a significant benefit here because the high levels of PpIX that normally accumulate during long ALA preincubations with conventional PDT (c-PDT), and which drive PpIX diffusion into nerve endings (25,28,31,(34)(35)(36), do not occur with the daylight regimen (33). We recently completed a clinical trial at Cleveland Clinic that applied this principle in an indoor environment, using an artificial light source (Blu-U TM ) to simulate daylight PDT for ALA-PDT of actinic keratosis in patients (37). We call this new regimen "painless PDT" (p-PDT).…”

Section: Introductionmentioning

confidence: 99%

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Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV‐induced Squamous Skin Pre‐cancer

Anand

Govande

Yasinchak

et al. 2020

Photochem & Photobiology

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Painless photodynamic therapy (p-PDT), which involves application of photosensitizer and immediate exposure to light to treat actinic keratosis (AK) in patients, causes negligible pain on the day of treatment but leads to delayed inflammation and effective lesion clearance (Kaw et al., J Am Acad Dermatol 2020). To better understand how p-PDT works, hairless mice with UV-induced AK were treated with p-PDT and monitored for 2 weeks. Lesion clearance after p-PDT was similar to clearance after conventional PDT (c-PDT). However, lesion biopsies showed minimal cell death and less production of reactive oxygen species (ROS) in p-PDT treated than in c-PDT-treated lesions. Interestingly, p-PDT triggered vigorous recruitment of immune cells associated with innate immunity. Neutrophils (Ly6G+) and macrophages (F4/ 80+) appeared at 4 h and peaked at 24 h after p-PDT. Damage-associated molecular patterns (DAMPs), including calreticulin, HMGB1, and HSP70, were expressed at maximum levels around 24 h post-p-PDT. Total T cells (CD3+) were increased at 24 h, whereas large increases in cytotoxic (CD8+) and regulatory (Foxp3+) T cells were observed at 1 and 2 weeks post-p-PDT. In summary, the ability of p-PDT to eliminate AK lesions, despite very little overt cellular damage, appears to involve stimulation of a local immune response.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV‐induced Squamous Skin Pre‐cancer

Anand

Govande

Yasinchak

et al. 2020

Photochem & Photobiology

Self Cite

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“…This unpleasant side effect occurs when patients undergo ALA preincubation for >1 h, probably due to diffusion of PpIX out of cancer cells and into nearby nerve endings (56). We recently described a new “painless” ALA‐PDT regimen for AK lesions of the face, in which pain is drastically reduced by eliminating the ALA preincubation step and instead administering topical ALA and illumination simultaneously (57). In the new regimen, ALA is applied to the skin and then the light is immediately switched on and left on for double the usual illumination period ( i.e.…”

Section: Clinical Trials Of Vitamin D As a Neoadjuvant For Ak/squamoumentioning

confidence: 99%

“…for 30 min rather than for 16 min 40 s). With this modified regimen, patients experience essentially no pain, yet cutaneous inflammation still develops (by ~ 24 h) and AK lesions are effectively cleared by 3 months post‐treatment (57). Recognizing that AK clearance is never 100% effective after a single treatment, for any ALA‐based PDT techniques whether “painless” or conventional, it would seem that adding a neoadjuvant such as 5‐FU or topical Vit D might be a reasonable way to improve AK clearance.…”

Section: Clinical Trials Of Vitamin D As a Neoadjuvant For Ak/squamoumentioning

confidence: 99%

Vitamin D and Other Differentiation‐promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer

Maytin

Hasan

2020

Photochem & Photobiology

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The efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA), which is preferentially taken up by cancerous cells and converted to protoporphyrin IX (PpIX), can be substantially improved by pretreating the tumor cells with vitamin D (Vit D). Vit D is one of several “differentiation‐promoting agents” that can promote the preferential accumulation of PpIX within the mitochondria of neoplastic cells, making them better targets for PDT. This article provides a historical overview of how the concept of using combination agents (“neoadjuvants”) for PDT evolved, from initial discoveries about neoadjuvant effects of methotrexate and fluorouracil to later studies to determine how vitamin D and other agents actually work to augment PDT efficacy. While this review focuses mainly on skin cancer, it includes a discussion about how these concepts may be applied more broadly toward improving PDT outcomes in other types of cancer.

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“…The conclusions suggested that the "simultaneous PDT" regimen is essentially painless with efficacy similar to conventional PDT. 6 Although the study was relatively small, and additional studies were recommended, the practical aspects of having bulbs illuminated for extended periods could prove financially prohibitive.…”

Section: Time and Temperaturementioning

confidence: 99%

Photodynamic Therapy in 2020: Lights in the Darkness

Bhatia

2020

J of Skin

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Photodynamic therapy (PDT) is an integral treatment modality for treating the entire process of photodamage, based on what is understood about the pathogenesis of actinic keratosis and the consequences from treating only visible spots and not the underlying disease. Dermatologists must consider incorporation of treatment in combination with duration, frequency, and tolerability of local skin reactions. These considerations are important, along with the combination of topical therapies and intermittent cryotherapy of individual actinic keratoses. Aside from costs and patient demographics, adaptation by dermatologists can influence variability in long-term treatment algorithms. There are multiple published guidelines and consensus statements for the US and Europe to promote safe incorporation of both blueand red light along with the variable concentrations of ALA by dermatologists. However, there is a lack of head to head studies and comparative superiority as well as any evidence to support the use of topical agents. As management of local skin reactions becomes more commonplace, so will improved management of PDT to foster patient safety.

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A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination

Cited by 38 publications

References 20 publications

Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV‐induced Squamous Skin Pre‐cancer

Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV‐induced Squamous Skin Pre‐cancer

Vitamin D and Other Differentiation‐promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer

Photodynamic Therapy in 2020: Lights in the Darkness

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