Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities

Willey, Andrea; Anderson, R. Rox; Sakamoto, Fumio

doi:10.1097/01.dss.0000452662.69539.57

Cited by 29 publications

(8 citation statements)

References 48 publications

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“…The increased PpIX fluorescence from RG2 tumors in vivo following hypothermia is expected from our in vitro studies but contrary to studies on skin demonstrating an increase PpIX accumulation at 38.5°C versus 29°C [ 33 ]. This may be attributable to the much lower temperature in that study; 29°C being considered outside the range of mild hypothermia and not examined in this work.…”

Section: Discussioncontrasting

confidence: 96%

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

et al. 2017

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BackgroundMalignant gliomas are highly invasive, difficult to treat, and account for 2% of cancer deaths worldwide. Glioblastoma Multiforme (GBM) comprises the most common and aggressive intracranial tumor. The study hypothesis is to investigate the modification of Photodynamic Therapy (PDT) efficacy by mild hypothermia leads to increased glioma cell kill while protecting normal neuronal structures.MethodsPhotosensitizer accumulation and PDT efficacy in vitro were quantified in various glioma cell lines, primary rat neurons, and astrocytes. In vivo studies were carried out in healthy brain and RG2 glioma of naïve Fischer rats. Hypothermia was induced at 1 hour pre- to 2 hours post-PDT, with ALA-PpIX accumulation and PDT treatments effects on tumor and normal brain PDT quantified using optical spectroscopy, histology, immunohistochemistry, MRI, and survival studies, respectively.FindingsIn vitro studies demonstrated significantly improved post-PDT survival in primary rat neuronal cells. Rat in vivo studies confirmed a neuroprotective effect to hypothermia following PpIX mediated PDT by T2 mapping at day 10, reflecting edema/inflammation volume reduction. Mild hypothermia increased PpIX fluorescence in tumors five-fold, and the median post-PDT rat survival time (8.5 days normothermia; 14 days hypothermia). Histology and immunohistochemistry show close to complete cellular protection in normal brain structures under hypothermia.ConclusionsThe benefits of hypothermia on both normal neuronal tissue as well as increased PpIX fluorescence and RG2 induced rat survival strongly suggest a role for hypothermia in photonics-based surgical techniques, and that a hypothermic intervention could lead to considerable patient outcome improvements.

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Section: Discussioncontrasting

confidence: 96%

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

et al. 2017

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“…hands, arms, legs, chest) [24] and may represent a reduced barrier to ALA distribution, and in turn increased PpIX production in the face. Second, skin temperature may be lower on extremities than on the face, resulting in lower PpIX generation on the arms and legs [25]. The observed differences in PpIX generation also appear to be patient-specific, with a correlation observed between PpIX concentration in AK lesions and normal locations on a per-patient basis.…”

Section: Discussionmentioning

confidence: 99%

Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy

Kanick

Davis

Zhao

et al. 2015

Photodiagnosis and Photodynamic Therapy

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Background Although Aminolevulinic Acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT. Methods A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48–76 hours after treatment (n=13). Results PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥ 5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p<0.022) (n=70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n=13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r=0.17, p<0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r=0.55, p < 0.051) and erythema (r=0.58, p < 0.039) in the 48–72 hr following treatment. Conclusions These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes.

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“…Recently, Willey et al [16] reported the efficacy and tolerability of temperature-modulated PDT for the treatment of AKs on the extremities. The upper and/or lower extremities of 20 subjects were treated with 20% ALA-PDT.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Photodynamic therapy in dermatology beyond non-melanoma cancer: An update

Wen

Hamblin

2017

Photodiagnosis and Photodynamic Therapy

162

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Photodynamic therapy (PDT) employs a photosensitizer (PS) and visible light in the presence of oxygen, leading to production of cytotoxic reactive oxygen species, which can damage the cellular organelles and cause cell death. In dermatology PDT has usually taken the form of topical application of a precursor in the heme biosynthesis pathway, called 5-aminolevulinic acid (or its methyl ester), so that an active PS, protoporphyrin IX accumulates in the skin. As PDT enhances dermal remodeling and resolves chronic inflamation, it has been used to treat cutaneous disorders include actinic keratoses, acne, viral warts, skin rejuvenation, psoriasis, localized scleroderma, some non-melanoma skin cancers and port-wine stains. Efforts are still needed to mitigate the side effects (principally pain) and improve the overall procedure.

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Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities

Abstract: Warming the skin during incubation of ALA seems to improve the efficacy of PDT in the treatment of AKs on the extremities and is well tolerated when heat application is controlled within the limits of safety.

Cited by 29 publications

References 48 publications

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy

Photodynamic therapy in dermatology beyond non-melanoma cancer: An update

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