Wearable devices for photodynamic therapy – A systematic review

Abstract

To the Editor: Photodynamic therapy (PDT) is a non-invasive treatment for premalignant and non-melanoma skin cancers.1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar PDT is an effective treatment modality, shown to have superior cosmetic outcomes and less morbidity compared to other non-surgical alternatives.2Moseley H. Allen J.W. Ibbotson S. et al.Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy.Br J Dermatol. 2006; 154: 747-750https://doi.org/10.1111/j.1365-2133.2006.07145.xCrossref PubMed Scopus (54) Google Scholar Conventional PDT involves the use of a photochemical reaction generated from the interaction of a photosensitizing agent, visible light, and oxygen to selectively destroy diseased tissues. However, the inconvenience of hospital-based treatment and associated discomfort are significant drawbacks.3Attili S.K. Lesar A. McNeill A. et al.An open pilot study of ambulatory photodynamic therapy using a wearable low-irradiance organic light-emitting diode light source in the treatment of nonmelanoma skin cancer.Br J Dermatol. 2009; 161: 170-173https://doi.org/10.1111/j.1365-2133.2009.09096.xCrossref PubMed Scopus (112) Google Scholar While daylight PDT circumvents the inconvenience of conventional PDT, it is limited by several variables including patient compliance and dependence on weather conditions. As such, great interest has been placed in developing wearable devices, which can potentially provide more consistent irradiation4Fonda-Pascual P. Alegre-Sánchez A. Harto-Castaño A. et al.Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.Photodiagnosis Photodyn Ther. 2019; 25: 136-141https://doi.org/10.1016/j.pdpdt.2018.11.018Crossref PubMed Scopus (7) Google Scholar and on-demand treatment. Recent studies have emerged to evaluate novel protocols and light sources to improve the delivery of PDT, including wearable devices. To evaluate the usefulness of such devices in the treatment of premalignant and non-melanoma skin cancers, a literature search was conducted (Fig 1). We report 6 studies involving 274 participants that explored the use of wearable devices to deliver PDT (Table I).Table IStudies reporting on the use of wearable devices for delivery of photodynamic therapy∗Non-malignant skin conditions are out of scope in this review.Reference & location of StudyStudy designNo. of patientsSkin diseaseDevice/type of lightTreatment protocolOutcome measuresClearanceAdverse effectslimitationsFonda-Pascual et al,4Fonda-Pascual P. Alegre-Sánchez A. Harto-Castaño A. et al.Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.Photodiagnosis Photodyn Ther. 2019; 25: 136-141https://doi.org/10.1016/j.pdpdt.2018.11.018Crossref PubMed Scopus (7) Google Scholar 2019SpainPilot27Actinic keratosis (AK)Wearable cap-like device/light-emitting diodeSingle cycle of 15 min (total light dose 4.59 J/cm2)Reduction in number of lesions; AK Quality of Life (AKQOL) score71% reduction in number of lesions at 2 moPain:None reportedOther adverse effects:Mild heat (25%), mild paraesthesia (7%)Small sample size; no control groupShort follow up time (2 mo)No blinded assessmentWearable device but not portableKessels et al,1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar 2017NetherlandsRetrospective125Superficial BCCAmbulight device/inorganic light-emitting diode3 h per cycle (total light dose 75 J/cm2); total number of cycles not specifiedPrimary outcome measure: 1-y probability of remaining tumour-freeSecondary outcome measures: (1) cumulative probability of recurrence-free survival at 6 and 18 mo(2) Incidence of adverse events100% complete clearance (no residual tumour) at 3 mo93.6% no recurrence at 6 mo, 89.9% at 12 mo, and 87.6% at 18 moNot reportedPain:None reportedOther adverse effects:Blistering and erosions (1 patient), bacterial skin infection (1 patient)Retrospective study with no control group; available information limited in some casesDevice unable to treat tumours on convex or concave areasLimited to tumours <2 cmMoseley et al,2Moseley H. Allen J.W. Ibbotson S. et al.Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy.Br J Dermatol. 2006; 154: 747-750https://doi.org/10.1111/j.1365-2133.2006.07145.xCrossref PubMed Scopus (54) Google Scholar 2006United KingdomPilot5Bowen’s DiseasePrototype device/light-emitting diode2 cycles (duration not specified, total light dose 75 J/cm2), 4 wk apartClearance and pain80% complete clearance at 6-13 mo follow-up time (median 9 mo)Pain:No pain in 10%, mild in 70%, moderate in 20%Other adverse effects:Mild oedema and erythemaSmall sample size; no control groupAttili et al,3Attili S.K. Lesar A. McNeill A. et al.An open pilot study of ambulatory photodynamic therapy using a wearable low-irradiance organic light-emitting diode light source in the treatment of nonmelanoma skin cancer.Br J Dermatol. 2009; 161: 170-173https://doi.org/10.1111/j.1365-2133.2009.09096.xCrossref PubMed Scopus (112) Google Scholar 2009United KingdomPilot12Bowen’s disease, superficial BCC <2 cm diameterPrototype device/organic light-emitting diode2 cycles of 3 h each (total light dose 45-60 J/cm2 per cycle), 1 mo apartEfficacy of treatment at 3, 6, 9, and 12 mo; pain and discomfort58.3% complete clearance at 1 yPain:Pain score ≤2 on numeric rating scale (NRS)Other adverse effects:Nil reportedSmall sample size; no control groupIbbotson et al,5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar 2022Ninewells Hospital, United KingdomPilot53Bowen’s disease, superficial BCC (<2 mm thickness), AK ≤2 cm diameterAmbulight device/inorganic light-emitting diode2 cycles of 3 h each (total light dose 75 J/cm2 per cycle), 1 wk apart for BCC/bowen's1 cycle of 3 h for actinic keratosis, second cycle given only if no clearance at 3 moPain and efficacy84% complete clearance at 1 yPain:Median NRS pain score 2 for first treatment; 4 for second treatmentOther adverse effects:Nil reportedSmall sample sizeDevice unable to treat tumours on convex or concave areasIbbotson et al,5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar 2022Ninewells Hospital, United KingdomRandomized controlled32Bowen’s disease, superficial BCC (≤2 cm diameter)Ambulight device/inorganic light-emitting diode2 cycles of 3 h each (total light dose 75 J/cm2 per cycle), 1 wk apart. second cycle given at 12 wk if no clearancePrimary outcome measure: painSecondary outcome measures: efficacy, erythema, patient satisfaction77.8% complete clearance with Ambulight vs 84.4% with conventional PDT at 1 yPain:1.25 for Ambulight vs 5.26 for conventional PDT on VASOther adverse effects:Erythema (slightly greater with Ambulight compared to conventional PDT)Small sample sizeDevice unable to treat tumours on convex or concave areasAK, Actinic keratosis; BCC, basal cell carcinoma; PDT, photodynamic therapy; VAS, visual analog scale.∗ Non-malignant skin conditions are out of scope in this review. Open table in a new tab AK, Actinic keratosis; BCC, basal cell carcinoma; PDT, photodynamic therapy; VAS, visual analog scale. Pilot studies using the Ambulight device (Ambicare Health) for the treatment of superficial basal cell carcinoma, Bowen’s disease and actinic keratoses, have reported up to 77.8% to 89.9% clearance at 1 year.1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar,5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar Preliminary studies suggest that the efficacy of these novel devices can be explained by the use of light sources that provide lower irradiance over a longer period. However, this has greater photobleaching efficacy and is potentially more cytotoxic.1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar The lower irradiance may also account for the lower pain scores reported with such wearable devices. Ibbotson et al reported a lower pain score of 1.25 with ambulatory PDT, compared to 5.26 with conventional PDT on the visual analog scale.5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar This was consistent with the overall low pain scores reported across the identified studies. Other reported symptoms include mild oedema and erythema,2Moseley H. Allen J.W. Ibbotson S. et al.Ambulatory photodynamic therapy: a new concept in delivering photodynamic therapy.Br J Dermatol. 2006; 154: 747-750https://doi.org/10.1111/j.1365-2133.2006.07145.xCrossref PubMed Scopus (54) Google Scholar,5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar while Fonda et al reported mild heat in 25% and mild paraesthesia in 7% of patients with their cap-like device.4Fonda-Pascual P. Alegre-Sánchez A. Harto-Castaño A. et al.Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.Photodiagnosis Photodyn Ther. 2019; 25: 136-141https://doi.org/10.1016/j.pdpdt.2018.11.018Crossref PubMed Scopus (7) Google Scholar Devices such as Ambulight are designed to turn on and off automatically, providing greater ease of use for patients and potentially improving compliance.1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar,5Ibbotson S.H. Ferguson J. Moseley H. Samuel I.D.W. Lesar A. Dawe R.S. A randomized assessor-blinded comparison of low-irradiance and conventional-irradiance photodynamic therapy for superficial basal cell carcinoma and Bowen disease.Br J Dermatol. 2022; 186: 577-579https://doi.org/10.1111/bjd.20762Crossref PubMed Scopus (1) Google Scholar However, findings are limited to mostly pilot studies with a short follow-up time, and a lack of control for comparison. Current wearable devices have significant drawbacks—these can only be used on flat body surfaces, limited to small lesions (less than 2 cm),1Kessels J. Dzino N. Nelemans P.J. Mosterd K. Kelleners-Smeets N.W.J. Ambulatory photodynamic therapy for superficial basal cell carcinoma: an effective light source?.Acta Derm Venereol. 2017; 97: 649-650https://doi.org/10.2340/00015555-2610Crossref PubMed Scopus (3) Google Scholar and peripheral margin failure.3Attili S.K. Lesar A. McNeill A. et al.An open pilot study of ambulatory photodynamic therapy using a wearable low-irradiance organic light-emitting diode light source in the treatment of nonmelanoma skin cancer.Br J Dermatol. 2009; 161: 170-173https://doi.org/10.1111/j.1365-2133.2009.09096.xCrossref PubMed Scopus (112) Google Scholar More data regarding cost are also required, as this can significantly influence patients’ decisions on treatment options. Further refinements on the design of such devices should be considered, with the aim of creating a lightweight, comfortable device that delivers consistent irradiation for remote PDT. In conclusion, given the significant burden of disease of premalignant and malignant skin diseases, delivery of ambulatory PDT via wearable devices can potentially be a feasible, convenient, and more comfortable method of treatment. Future efforts may be devoted to the development of devices that allow for remote and reliable delivery of PDT. None disclosed.