Randomized clinical trial testing the efficacy and safety of 0.5% colchicine cream versus photodynamic therapy with methyl aminolevulinate in the treatment of skin field cancerization: study protocol.

BACKGROUND: The primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization. METHODS: In a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant. DISCUSSION: It is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results. TRIAL REGISTRATION: The trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9 , date assigned May 4, 2016, retrospectively registered).

Preliminary efficacy and safety analysis: 12-month results in 83 patients using a novel approach of widefield radiation therapy for extensive skin field cancerization with or without keratinocyte cancers.

PURPOSE: Evaluate the use of widefield radiation therapy (RT) in the management of extensive skin field cancerization (ESFC) with/without keratinocyte cancer (KC). METHODS: The National Dermatology Radiation Oncology Registry is a multidisciplinary collaboration (dermatologists and radiation oncologists). It captures disease description, prior therapies, radiation prescription, clinical effect, skin cosmesis scores, and toxicity data. This analysis included 12-month follow-up data on 89 treated fields from a subset of 83 patients. RESULTS: Clinical success (>90% field clearance) was 96% (ESFC, n = 63) and 88% (ESFC with KC, n = 26). Complete lesion response was seen in 96% of evaluable (n = 25) ESFC with KC. Recurrence (4/89 [5%]) and appearance of new lesions (10/89 [11%]) were minimal. Cosmetic outcome was excellent/good in 98% ESFC and 96% ESFC with KC. Grade 1-2 acute radiation dermatitis occurred in up to 80% of treated fields. The frequency of Grade 3 acute skin toxicities was low. CONCLUSIONS: Registry data demonstrate the potential for widefield RT to treat patients with significant skin pathology who have exhausted other therapies and require durable, minimally invasive treatment options. At 12 months, observed clinical success rates were higher than those reported for topical interventions for ESFC. Ongoing follow-up is required to determine longer term outcomes.

Cold Atmospheric Plasma (CAP) for the Treatment of Actinic Keratosis and Skin Field Cancerization: Clinical and High-Frequency Ultrasound Evaluation.

INTRODUCTION: Cold atmospheric plasma (CAP) has been clinically demonstrated to be an effective treatment for actinic keratosis (AK) in a number of case series. In this study, we evaluated the efficacy of CAP in the treatment of multiple AKs and assessed morphological changes induced on the skin field of cancerization both clinically and by high-frequency ultrasound (HFUS). METHODS: Patients with multiple grade I-II AKs of the scalp and/or face who were resistant or intolerant to conventional field-directed treatments were enrolled. CAP treatments were performed using a microwave-driven argon plasma jet. At baseline and 3 months after the last CAP session, performance indexes were determined using three-dimensional digital pictures and HFUS investigations were performed on a representative Olsen grade II AK and a small spot of clinically unaffected skin within the test area. RESULTS: Twelve patients were enrolled in the study. All clinical variables showed a statistically significant reduction after CAP. HFUS evaluation revealed that the total, epidermal and dermal thicknesses of the target AKs had not changed with treatment. CAP therapy significantly increased dermal density in both the target AK and the surrounding photodamaged skin and signficantly decreased the thickness of the subepidermal low-echogenic band in the perilesional skin, which is an ultrasound sign of photodamage. CONCLUSIONS: Cold atmospheric plasma was found to be an effective treatment for patients with multiple AKs. CAP was not followed by skin atrophy. HFUS examiniation showed the CAP improved features of chronic photodamage of the dermis of the skin underlying and surrounding the AK spots.

Comparison of clinical and histologic findings in daylight photodynamic therapy for skin field cancerization: A randomized controlled four-arm study on physical methods-assisted delivery of methyl aminolevulinate.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has similar efficacy to conventional photodynamic therapy in treating actinic keratosis (AKs). Good clinical outcomes have been reported when associated with physical methods such as microneedles, but a comparison of different methods and histologic studies is lacking. OBJECTIVES: To evaluate clinical and histologic modifications induced by standard DL-PDT and compare with DL-PDT associated with physical methods in treating skin field cancerization of the face. METHODS: Forty patients with photodamaged skin and at least one AK lesion on the face were randomly distributed into four groups, ten patients in each (I: Standard DL-PDT; II: DL-PDT + microneedles; III: DL-PDT + CO2 laser; IV: DL-PDT + microdermabrasion) and underwent two DL-PDT sessions with methyl aminolevulinate cream and 2-hour daylight exposure. Skin biopsies were performed on all patients before and 3 months after. All fragments were stained using the hematoxylin-eosin, orcein, and picrosirius. RESULTS: All 40 patients completed the study. Group III had a higher AK-clearance after 1 (p = 0,002) and 3 (p = 0,034) months, but it was similar in every group at 6 months (p = 0,441). Group III and IV had better clinical global improvement on texture, pigmentation and fine lines. In the groups associated with physical methods, the improvement of the keratinocytes' atypia and solar elastosis were remarkable. Only group III showed a significant reduction in solar elastosis (p = 0.034) and increased collagen type I (p = 0.028) after treatment. CONCLUSION: DL-PDT-associated with physical methods had better clinical and histologic results. AK-clearance were significantly higher after 1 and 3 months with pretreatment-CO2 laser. Photorejuvenation were more evident with pretreatment-CO2 laser and microdermabrasion. Pretreatment-CO2 laser showed a significant reduction in solar elastosis and increase of collagen type 1. These results pointed to the pretreatment with laser as a potentially better option for skin field cancerization of the face.

Laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound with short incubation time for field cancerization treatment: A left-right comparison.

BACKGROUND: Laser-assisted MAL-PDT has been reported to increase the effectiveness of conventional PDT. Nonetheless, clinical effects of this association when reducing MAL incubation time is poorly discussed. Furthermore, the association of acoustic pressure wave ultrasound with laser-assisted MAL-PDT with short incubation time for field cancerization had not been reported before. OBJECTIVES: To compare clinical effects of ablative fractional laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound (IMPACT US) with 1-hour incubation time and conventional MAL-PDT for skin field cancerization on the forearms, as well as the impact on safety and tolerability. METHODS: Fifteen patients with 638 AK (grade I-III) with field cancerized-skin on the forearms were enrolled in this left-right trial. Two protocols were randomly chosen. One side was treated with conventional MAL-PDT, whereas the other with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound with 1-hour incubation time. Actinic keratoses were quantitively measured, and the other signs of sun-damaged skin, like pigmentation and texture, in field cancerized skin were qualitatively evaluated before and after six months. Side effects were assessed subjectively during the procedure and one week after. RESULTS: All patients completed the study. At six months after treatment, both protocols reduced the number of AK (72%; CO2 + PDT, and 65%; MAL-PDT). The difference between these two protocols was not statistically significant (p = 0.77). The improvement of pigmentation and texture of field cancerized skin was more significant on the side treated with laser-assisted MAL-PDT associated with acoustic pressure wave ultrasound. Both protocols were well tolerated and without significant difference in adverse events. CONCLUSION: Laser-assisted MAL-PDT using CO2 laser and acoustic pressure wave ultrasound with short incubation time of 1 h was as effective as conventional MAL-PDT for field-cancerized skin with actinic keratosis in forearms with better cosmetic outcome.