Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial.

BACKGROUND: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. METHODS: In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used. RESULTS: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P = .0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P = .00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome. CONCLUSIONS: Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.

Long-Term Efficacy of Photodynamic Therapy with Fractionated 5-Aminolevulinic Acid 20% versus Conventional Two-Stage Topical Methyl Aminolevulinate for Superficial Basal-Cell Carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is a noninvasive treatment for patients with superficial basal-cell carcinoma (sBCC). The efficacy of PDT may vary with different photosensitizers and treatment schedules. OBJECTIVE: Our objective was to evaluate whether fractionated 5-aminolevulinic acid 20% (ALA)-PDT is superior to conventional two-stage methyl aminolevulinate (MAL)-PDT for sBCC. METHODS: We present the 5 years results of a single-blind, randomized, multicenter trial. 162 patients with a histologically confirmed primary sBCC were randomized to fractionated ALA-PDT or MAL-PDT. RESULTS: The 5-year tumor-free survival rate was 70.7% (95% CI 58.2-80.1%) for ALA-PDT and 76.5% (95% CI 64.4-85.0%) for MAL-PDT. In the first 3 years, there was no significant difference in risk of treatment failure (HR = 1.53, p = 0.283), but in the long-term, the risk of recurrence was significantly lower following MAL-PDT compared to ALA-PDT (HR = 0.125, p = 0.049). As judged by patients, the esthetic result was good-excellent in 96.8% (61/63) and 94.4% (56/59) of patients treated with ALA-PDT and MAL-PDT, respectively (p = 0.631). CONCLUSION: The long-term efficacy is significantly higher for conventional two-stage MAL-PDT than for fractionated ALA-PDT, whereas there was no significant difference in esthetic outcome between the treatments at 5 years after treatment. These results indicate that fractionated ALA-PDT offers no benefit over conventional two-stage MAL-PDT.

Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Treatment of actinic keratosis (AK) aims to prevent cutaneous squamous cell carcinoma (cSCC). However, whether AK can progress into invasive cSCC is a matter of debate, and little is known about the effect of treatment on preventing cSCC. Objectives: To evaluate the risk of invasive cSCC and factors that may contribute to increased risk in patients with multiple AKs. Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, 624 patients with a minimum of 5 AKs within an area of 25 to 100 cm2 on the head were recruited from the Department of Dermatology of 4 hospitals in the Netherlands. Long-term follow-up was performed from July 1, 2019, to December 31, 2020. Interventions: Patients were randomized to treatment with 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. Main Outcomes and Measures: The primary outcome was the proportion of patients with invasive cSCC in the target area during follow-up. Secondary outcomes were the associations between risk of invasive cSCC and a priori defined potential prognostic factors, including type of treatment, severity of AK (Olsen grade), history of nonmelanoma skin cancer, and additional treatment. Results: Of the 624 patients (558 [89.4%] male; median age, 73 years [range, 48-94 years]) in the study, 26 were diagnosed with a histologically proven invasive cSCC in the target area during follow-up. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK (Olsen grade III), the risk was 20.9% (95% CI, 10.8%-38.1%), and the risk was especially high (33.5%; 95% CI, 18.2%-56.3%) in patients with severe AK who needed additional treatment. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, risk of invasive cSCC was highest in patients with Olsen grade III AK and was substantially increased in patients who received additional treatment. These patients should be closely followed up after treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT02281682.

[Woman with a yellow patch on the hairy part of the head]. / Een vrouw met een gele plek op het behaarde hoofd.

A 52-year-old woman was referred to a dermatologist with a changed yellowish lesion on her scalp. Histological features were those of a sebaceous naevus with secondary malignant differentiation into superficial and solid basal cell carcinoma. A sebaceous naevus is a benign, congenital, hamartomatous lesion. In adulthood, secondary neoplasms may develop within them.

Exploration of Patient Characteristics and Quality of Life in Patients with Lipoedema Using a Survey.

INTRODUCTION: Lipoedema is a chronic disorder in which excessive fat distribution occurs predominantly from the waist down, resulting in a disproportion between the lower extremities and upper torso. Lipoedema is often not recognized, while patients experience pain and easy bruising. As a long-term condition, lipoedema has a massive effect on patients' lives and mental health. The aim of this study is to explore patient characteristics, quality of life, physical complaints and comorbidities in patients with lipoedema. METHODS: A survey was conducted by email amongst lipoedema patients, consisting of informed consent and multiple questionnaires. The questionnaires included general patient characteristics, physical complaints, comorbidities, RAND-36 and EQ-5D-3L. Participants who responded to a message on the Dutch Lipoedema Association website were recruited. RESULTS: All lipoedema patients experience physical complaints, with pain (88.3 %) and easy bruising (85.9 %) as primary complaints. The diagnosis was mostly made by a dermatologist after visiting a mean of 2.8 doctors. Furthermore, mean time from onset until diagnosis was 18 years. Quality of life (59.3) was significantly lower than the Dutch female average (74.9; p < 0.001). Additionally, patients with comorbidities had significant lower quality of life (RAND 54.7, p < 0.001). CONCLUSIONS: Lipoedema patients often have severe complaints and experience lower quality of life regarding physical, emotional and social functioning. Additionally, comorbidities have a large impact on quality of life.

Three-Year Follow-Up Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Noninferiority, Randomized Controlled Trial.

A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8-66.9), 79.7% for imiquimod (95% CI = 71.6-85.7), and 68.2% for fluorouracil (95% CI = 58.1-76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33-0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51-1.05, P = 0.092) and 0.68 (95% CI = 0.44-1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.

Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial.

BACKGROUND: Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma. METHODS: In this single blind, non-inferiority, randomised controlled multicentre trial, we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherlands. Patients were randomly assigned to receive treatment with methylaminolevulinate photodynamic therapy (MAL-PDT; two sessions with an interval of 1 week), imiquimod cream (once daily, five times a week for 6 weeks), or fluorouracil cream (twice daily for 4 weeks). Follow-up was at 3 and 12 months post-treatment. Data were collected by one observer who was blinded to the assigned treatment. The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up. A pre-specified non-inferiority margin of 10% was used and modified intention-to-treat analyses were done. This trial is registered as an International Standard Randomised controlled trial (ISRCTN 79701845). FINDINGS: 601 patients were randomised: 202 to receive MAL-PDT, 198 to receive imiquimod, and 201 to receive fluorouracil. A year after treatment, 52 of 196 patients treated with MAL-PDT, 31 of 189 treated with imiquimod, and 39 of 198 treated with fluorouracil had tumour residue or recurrence. The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8% (95% CI 66.8-79.4) for MAL-PDT, 83.4% (78.2-88.9) for imiquimod cream, and 80.1% (74.7-85.9) for fluorouracil cream. The difference between imiquimod and MAL-PDT was 10.6% (95% CI 1.5-19.5; p=0.021) and 7.3% (-1.9 to 16.5; p=0.120) between fluorouracil and MAL-PDT, and between fluorouracil and imiquimod was -3.3% (-11.6 to 5.0; p=0.435. For patients treated with MAL-PDT, moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session. For other local adverse reactions, local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with MAL-PDT. In the MAL-PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting. INTERPRETATION: Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma. On the basis of these findings, imiquimod can be considered the preferred treatment, but all aspects affecting treatment choice should be weighted to select the best treatment for patients. FUNDING: Grant of the Netherlands Organization for Scientific Research ZONMW (08-82310-98-08626).

Physical activity and adherence to compression therapy in patients with venous leg ulcers.

OBJECTIVE: To assess levels of physical activity, particularly walking and leg exercises, among patients with venous leg ulcers and the extent to which patients adhere to compression therapy. DESIGN: Descriptive cross-sectional study. SETTING: Patients from 12 outpatient dermatology clinics were invited to participate in this study. When they agreed, they were asked to wear an accelerometer for a week and were then interviewed at the outpatient clinic. Patients A total of 150 patients with leg ulcers caused mainly by venous insufficiency. MAIN OUTCOME MEASURES: The amount of moderately strenuous physical activity, the amount of walking, and adherence to compression therapy. RESULTS: In this study, 39% of the patients interviewed displayed adherence to compression therapy. Self-reported data validated by the use of an accelerometer indicated that the amount of moderately strenuous activity in the study group was low compared with that of the general Dutch population; 35% of the patients did not have a 10-minute walk even once a week. CONCLUSIONS: Low levels of physical activity were established in a group of 150 patients with venous leg ulcers. Full adherence to compression therapy was reported in about 40% of the patients. Patients should be educated and encouraged to (1) enhance physical activity through walking and leg exercises and (2) increase adherence to compression therapy.