Photodermatology, Photoimmunology & Photomedicine
ORIGINAL ARTICLE
Fractional carbon dioxide laser-assisted photodynamic therapy for patients with actinic keratosis Hyo Sang Song1, Soo-Eun Jung1, Yong Hyun Jang2, Hee Young Kang1, Eun-So Lee1 & You Chan Kim1
1
Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea. 2 Department of Dermatology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Background/purpose A relatively long incubation time is needed for photosensitizer absorption in conventional photodynamic therapy (PDT) for actinic keratosis (AK). The use of ablative CO2 fractional lasers (AFXLs) to increase drug delivery could shorten the incubation time. Here, we aimed to compare the efficacy between AFXLassisted PDT with a short incubation time and conventional PDT for AK.
Key words:
Methods Patients with histopathologically confirmed facial AK were randomly divided into two groups. The lesions were histopathologically classified into grades I–III. In the AFXL-assisted PDT group, an ablative fractional laser was used for pretreatment, prior to the application of methyl aminolevulinate, with an incubation time of 90 min. Irradiation was performed with a 630-nm light-emitting diode. In the conventional PDT group, the incubation time was 180 min. All the patients received two rounds of PDT at 2week intervals and underwent clinical or histological evaluation at 10 weeks after the first PDT course.
ablative carbon dioxide fractional laser; actinic keratosis; photodynamic therapy; short incubation time
Correspondence: You Chan Kim, M.D., Ph.D., Department of Dermatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon 443-380, Republic of Korea. Tel: +82 31 219 5190 Fax: +82 31 219 5189 e-mail: [email protected]
Accepted for publication: 16 January 2015
Conflicts of interest None declared.
Funding sources This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRK), funded by grant NRF-2013R1A1A2006944 to Y.C. Kim from the Ministry of Education, Science and Technology.
296
Results Twenty-two patients underwent conventional PDT and 24 patients underwent AFXL-assisted PDT. Thirty-four AKs were included in the conventional PDT group, and 35 AKs were included in the AFXL-assisted PDT group. The clearance rate was 64.7% in the conventional PDT and 71.4% in the AFXL-assisted PDT group; no significant differences in the clearance rate were noted between the groups (P = 0.55). The clearance rates for each grade also did not significantly differ between the two groups. Conclusions The use of AFXL before PDT reduced the incubation time, but yielded similar treatment efficacy as compared to conventional PDT. Photodermatol Photoimmunol Photomed 2015; 31: 296–301
ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd doi:10.1111/phpp.12184
Fractional laser-assisted PDT for AK
Topical photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is one of the common therapeutic modalities for actinic keratosis (AK) (1). MAL needs to penetrate through the epidermis and be converted to the photoactive fluorescent protoporphyrin IX (PpIX) in dysplastic cells. Because the accumulation of PpIX is greater in dysplastic cells than in normal cells, irradiation selectively destroys the abnormal cells through the production of reactive oxygen species (2). Thus, to achieve successful outcomes with PDT, sufficient accumulation of PpIX is necessary. Conventional PDT with MAL requires 3 h of incubation time. However, this relatively long time for incubation time makes causes patients discomfort. To enhance topical MAL delivery, ablative fractional lasers (AFXLs), including the carbon dioxide (CO2, 10 600 nm) and erbium-doped yttrium aluminum garnet (Er:YAG, 2940 nm) lasers, were designed as pretreatment modalities (3–6). Before PDT is initiated, an AFXL is used to produce microscopic vertical holes through the epidermis in order to accelerate the penetration and accumulation of PpIX (7). PpIX fluorescence in CO2-based AFXL-pretreated skin is more intense, and deeper penetration and more even distribution of PpIX is also observed (3, 6). Furthermore, in an animal study, the surface PpIX fluorescence at 60 min in AFXL-treated skin was significantly more intense than that in nontreated skin at 180 min (3). We conducted a pilot study to evaluate the efficacy of AFXL-assisted PDT, with an incubation period of 90 min, and observed that 70.6% of AKs showed complete response within 3 sessions of AFXL-assisted PDT – this therapeutic result is not inferior to that associated with conventional PDT (8). Therefore, in the present randomized study, we aimed to compare the efficacy between AFXL-assisted PDT with a short incubation time and conventional PDT for AK.
MATERIALS AND METHODS Patients Patients aged ≥18 years with histopathologically confirmed facial AKs were recruited from the Department of Dermatology, Ajou University Hospital. None of the subjects had previously undergone treatment for AK. The exclusion criteria were as follows: porphyria; use of photosensitive drugs or the presence of photoallergic dermatitis; known allergy to MAL cream; refusal to undergo PDT for any reason (i.e., preferred to be treated with cryotherapy or topical agents); and any conditions Photodermatol Photoimmunol Photomed 2015; 31: 296–301 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
associated with a risk of poor protocol compliance. The lesions were categorized into three grades according to the severity of dysplasia (9). The study was approved by the institutional review board (IRB) and research ethics committee at the Ajou University Hospital (IRB No.: MED-MDB-12-088).
Treatment protocol The treatment protocol is illustrated in Fig. 1. Patients with AK confirmed through a histological evaluation were randomized into either an AFXL-assisted or a conventional PDT group by the tossing of a coin. The number of AK lesions was also counted prior to irradiation in PDT. In the conventional PDT group, curettage was performed before the application of the photosensitizer. In the AFXL-assisted PDT group, pretreatment was administered using a single pass of ablative CO2 fractional laser (eCO2; Lutronic Inc., Seoul, South Korea). The laser parameters were as follows: wavelength of 10 600 nm, pulse energy of 50 mJ, spot density of 100 spots/cm2, power of 30W, and beam size of 120 lm. Thereafter, the patients in both groups applied the MAL cream (Metvix, Galderma, Sophia Antipolis, France) to the areas with the lesion and then covered the areas with an occlusive film (Tegaderm, 3M; Minneapolis, MN, USA). The incubation time was 180 min in the conventional PDT group and 90 min in the AFXLassisted PDT group (8). Subsequently, irradiation was performed with a 630-nm light-emitting diode (LED) from Aktilite CL 128 (Galderma), at a dose of 37 J/cm2 in both groups. All the patients received PDT at week 0 and week 2, followed by a clinical and histological evaluation at 10 weeks after the first course of PDT.
Evaluation of efficacy Two investigators evaluated the clinical and histological responses after the completion of the treatment sessions. Although all the patients were expected to undergo a final histological evaluation, some refused to undergo a skin biopsy because of cosmetic problems. The following definitions were used in this study: Clinical complete response (CR) refers to the complete removal of the lesion; partial response (PR) refers to a 25–99% reduction in lesion size; and non-response (NR) refers to a 0–24% reduction in lesion size. Histological CR was defined as the complete clearance of atypical keratinocytes, whereas IC was defined as the incomplete clearance of atypical keratinocytes. The clearance rate was calculated as follows: 297
Song et al.
Fig. 1. Schematic diagram and time schedule of the comparative study between conventional photodynamic therapy and ablative fractional CO2 laserassisted photodynamic therapy.
[(total number of lesions with clinical CR + histological CR)/ total number of lesions] 9 100.
Statistical analysis The chi-square test was used to analyze the categorical data (SPSS 20.0 software; SPSS Inc., Chicago IL, USA). Statistical significance was considered when the P value was
ORIGINAL ARTICLE
Fractional carbon dioxide laser-assisted photodynamic therapy for patients with actinic keratosis Hyo Sang Song1, Soo-Eun Jung1, Yong Hyun Jang2, Hee Young Kang1, Eun-So Lee1 & You Chan Kim1
1
Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea. 2 Department of Dermatology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Background/purpose A relatively long incubation time is needed for photosensitizer absorption in conventional photodynamic therapy (PDT) for actinic keratosis (AK). The use of ablative CO2 fractional lasers (AFXLs) to increase drug delivery could shorten the incubation time. Here, we aimed to compare the efficacy between AFXLassisted PDT with a short incubation time and conventional PDT for AK.
Key words:
Methods Patients with histopathologically confirmed facial AK were randomly divided into two groups. The lesions were histopathologically classified into grades I–III. In the AFXL-assisted PDT group, an ablative fractional laser was used for pretreatment, prior to the application of methyl aminolevulinate, with an incubation time of 90 min. Irradiation was performed with a 630-nm light-emitting diode. In the conventional PDT group, the incubation time was 180 min. All the patients received two rounds of PDT at 2week intervals and underwent clinical or histological evaluation at 10 weeks after the first PDT course.
ablative carbon dioxide fractional laser; actinic keratosis; photodynamic therapy; short incubation time
Correspondence: You Chan Kim, M.D., Ph.D., Department of Dermatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-Gu, Suwon 443-380, Republic of Korea. Tel: +82 31 219 5190 Fax: +82 31 219 5189 e-mail: [email protected]
Accepted for publication: 16 January 2015
Conflicts of interest None declared.
Funding sources This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRK), funded by grant NRF-2013R1A1A2006944 to Y.C. Kim from the Ministry of Education, Science and Technology.
296
Results Twenty-two patients underwent conventional PDT and 24 patients underwent AFXL-assisted PDT. Thirty-four AKs were included in the conventional PDT group, and 35 AKs were included in the AFXL-assisted PDT group. The clearance rate was 64.7% in the conventional PDT and 71.4% in the AFXL-assisted PDT group; no significant differences in the clearance rate were noted between the groups (P = 0.55). The clearance rates for each grade also did not significantly differ between the two groups. Conclusions The use of AFXL before PDT reduced the incubation time, but yielded similar treatment efficacy as compared to conventional PDT. Photodermatol Photoimmunol Photomed 2015; 31: 296–301
ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd doi:10.1111/phpp.12184
Fractional laser-assisted PDT for AK
Topical photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is one of the common therapeutic modalities for actinic keratosis (AK) (1). MAL needs to penetrate through the epidermis and be converted to the photoactive fluorescent protoporphyrin IX (PpIX) in dysplastic cells. Because the accumulation of PpIX is greater in dysplastic cells than in normal cells, irradiation selectively destroys the abnormal cells through the production of reactive oxygen species (2). Thus, to achieve successful outcomes with PDT, sufficient accumulation of PpIX is necessary. Conventional PDT with MAL requires 3 h of incubation time. However, this relatively long time for incubation time makes causes patients discomfort. To enhance topical MAL delivery, ablative fractional lasers (AFXLs), including the carbon dioxide (CO2, 10 600 nm) and erbium-doped yttrium aluminum garnet (Er:YAG, 2940 nm) lasers, were designed as pretreatment modalities (3–6). Before PDT is initiated, an AFXL is used to produce microscopic vertical holes through the epidermis in order to accelerate the penetration and accumulation of PpIX (7). PpIX fluorescence in CO2-based AFXL-pretreated skin is more intense, and deeper penetration and more even distribution of PpIX is also observed (3, 6). Furthermore, in an animal study, the surface PpIX fluorescence at 60 min in AFXL-treated skin was significantly more intense than that in nontreated skin at 180 min (3). We conducted a pilot study to evaluate the efficacy of AFXL-assisted PDT, with an incubation period of 90 min, and observed that 70.6% of AKs showed complete response within 3 sessions of AFXL-assisted PDT – this therapeutic result is not inferior to that associated with conventional PDT (8). Therefore, in the present randomized study, we aimed to compare the efficacy between AFXL-assisted PDT with a short incubation time and conventional PDT for AK.
MATERIALS AND METHODS Patients Patients aged ≥18 years with histopathologically confirmed facial AKs were recruited from the Department of Dermatology, Ajou University Hospital. None of the subjects had previously undergone treatment for AK. The exclusion criteria were as follows: porphyria; use of photosensitive drugs or the presence of photoallergic dermatitis; known allergy to MAL cream; refusal to undergo PDT for any reason (i.e., preferred to be treated with cryotherapy or topical agents); and any conditions Photodermatol Photoimmunol Photomed 2015; 31: 296–301 ª 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
associated with a risk of poor protocol compliance. The lesions were categorized into three grades according to the severity of dysplasia (9). The study was approved by the institutional review board (IRB) and research ethics committee at the Ajou University Hospital (IRB No.: MED-MDB-12-088).
Treatment protocol The treatment protocol is illustrated in Fig. 1. Patients with AK confirmed through a histological evaluation were randomized into either an AFXL-assisted or a conventional PDT group by the tossing of a coin. The number of AK lesions was also counted prior to irradiation in PDT. In the conventional PDT group, curettage was performed before the application of the photosensitizer. In the AFXL-assisted PDT group, pretreatment was administered using a single pass of ablative CO2 fractional laser (eCO2; Lutronic Inc., Seoul, South Korea). The laser parameters were as follows: wavelength of 10 600 nm, pulse energy of 50 mJ, spot density of 100 spots/cm2, power of 30W, and beam size of 120 lm. Thereafter, the patients in both groups applied the MAL cream (Metvix, Galderma, Sophia Antipolis, France) to the areas with the lesion and then covered the areas with an occlusive film (Tegaderm, 3M; Minneapolis, MN, USA). The incubation time was 180 min in the conventional PDT group and 90 min in the AFXLassisted PDT group (8). Subsequently, irradiation was performed with a 630-nm light-emitting diode (LED) from Aktilite CL 128 (Galderma), at a dose of 37 J/cm2 in both groups. All the patients received PDT at week 0 and week 2, followed by a clinical and histological evaluation at 10 weeks after the first course of PDT.
Evaluation of efficacy Two investigators evaluated the clinical and histological responses after the completion of the treatment sessions. Although all the patients were expected to undergo a final histological evaluation, some refused to undergo a skin biopsy because of cosmetic problems. The following definitions were used in this study: Clinical complete response (CR) refers to the complete removal of the lesion; partial response (PR) refers to a 25–99% reduction in lesion size; and non-response (NR) refers to a 0–24% reduction in lesion size. Histological CR was defined as the complete clearance of atypical keratinocytes, whereas IC was defined as the incomplete clearance of atypical keratinocytes. The clearance rate was calculated as follows: 297
Song et al.
Fig. 1. Schematic diagram and time schedule of the comparative study between conventional photodynamic therapy and ablative fractional CO2 laserassisted photodynamic therapy.
[(total number of lesions with clinical CR + histological CR)/ total number of lesions] 9 100.
Statistical analysis The chi-square test was used to analyze the categorical data (SPSS 20.0 software; SPSS Inc., Chicago IL, USA). Statistical significance was considered when the P value was
