Successful treatment of Bowen's Disease in the nipple-areola complex with a combination of photodynamic therapy and cryotherapy-A case report.

Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.

Photodynamic therapy with BF-200 ALA gel for the treatment of actinic keratosis, Bowen´s disease and basal cell carcinoma in long term immunosuppressed patients after organ transplantation.

Continuous immunosuppression after organ transplantation is associated with an increased risk of developing keratinocyte neoplastic lesions. Topical photodynamic therapy represents a therapeutic approach for different keratinocyte neoplastic lesions. However, the specific efficacy and safety of this treatment in this immunocompromised population remains largely unknown. In this case report series, we show the efficacy and safety of photodynamic therapy with BF-200 ALA gel using red-light and daylight in immunocompromised patients. Out of 8 patients presented here, 1 was treated for 8 basal cell carcinomas, 1 for 2 Bowen´s disease lesions and 6 were treated for field cancerization including 4 to 10 actinic keratoses. Treatment response rates were above 75 %. The adverse events, including pain, did not differ from those already described for PDT. These data suggest that PDT with BF-200 ALA gel could be an effective and safe option to add to the treatment portfolio for neoplastic keratinocyte lesions in this high-risk population.

Bowen's disease of the vulva and perianal area in a SLE patient successfully treated with Photodynamic therapy: A case report.

Photodynamic therapy (PDT) has emerged as a non-invasive treatment modality for superficial skin cancers. It has the advantage of greater tolerance and providing better cosmetic outcomes than conventional treatment methods. Because of the rarity of extensive Bowen's disease located in the genital area, evidence of efficacy for therapies is mainly based on case reports and clinical experience. This report presents a case of a 32-year-old female with Bowen's disease of the vulva and perianal area with systemic lupus erythematosus successfully treated by 5-aminolaevulinic acid PDT. There was no evidence of recurrence after five-years of follow-up.

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.

Cryosurgery and 5-Fluorouracil Combination Therapy for Treatment of Bowen's Disease and Superficial Basal Cell Carcinoma.

BACKGROUND: Non-melanoma skin cancer (NMSC), which includes both Bowen's disease (BD) and superficial basal cell carcinoma (sBCC), is the most commonly diagnosed cancer in Canada. BD and sBCC are amenable to minimally invasive treatments however, large-scale studies assessing long-term outcomes are lacking, particularly regarding the timing and duration of non-invasive combination treatments. OBJECTIVE: Examine the clinical cure rate of BD and sBCC using a combination treatment consisting of a single cycle of cryotherapy followed by a three to four-week course of topical 5-fluorouracil (5-FU). METHODS: Retrospective chart review at a single center. Inclusion criteria included histology-proven sBCC or BD treated with either a combination protocol, cryosurgery, or 5-FU alone. RESULTS: 310 biopsy-confirmed cases of BD and 176 biopsy-confirmed cases of sBCC were analyzed. Of these, 229 cases of BD and 61 cases of sBCC were treated with cryosurgery and immediate 5-FU application, yielding a clearance rate of 90% and 86.9% at 6 months from initial treatment. CONCLUSION: Cryosurgery followed by immediate 5-FU use may be an effective mode of treatment for BD and sBCC, negating the need for invasive procedures and allowing for increased accessibility. Further studies with longer follow-up intervals, comparisons with other non-invasive treatments, and evidence of histologic cure are required. J Drugs Dermatol. 2023;22(12):1166-1171. doi:10.36849/JDD.7378.

Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

Successful treatment of extremely large Bowen's disease lesion by topical photodynamic therapy and imiquimod: Using optical coherence tomography to detect early recurrence loci and validate the cure.

Bowen's disease, a form of skin cancer, is an intraepithelial carcinoma involving keratinocytes. It is associated with a risk of developing invasive squamous cell carcinoma in 3-5% of cases. Ultraviolet exposure, arsenic, human papillomavirus infection, immunosuppression, and genetic factors have been reported to be the causes. Clinically, it presents as symptomless and slowly growing, well-demarcated, irregular erythematous patches or plaques with scaly or crusted surfaces. Surgical excision remains common; however, for large (>20 mm) or multiple Bowen's disease lesions, alternative therapies need to be considered. Here, we present a case of extremely large Bowen's disease lesions in the lower extremities successfully treated with combination therapy using topical aminolevulinic acid-based photodynamic therapy followed by topical 5% imiquimod cream. Optical coherence tomography revealed disorganized and uneven nuclei of keratinocytes in the recurrent lesions, which became relatively small and uniform upon resolution. We demonstrated that photodynamic therapy provides a generally safe and effective strategy for treating large Bowen's disease lesions and optical coherence tomography provides a useful and noninvasive diagnosis of early Bowen's disease recurrence.

Durable Clearance Rate of Photodynamic Therapy for Bowen Disease and Cutaneous Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Although surgery is the treatment of choice for Bowen disease (BD) and cutaneous squamous cell carcinoma (cSCC), nonsurgical treatments such as photodynamic therapy (PDT) may be preferred for select tumors. Previous meta-analysis have failed to gather strong evidence to recommend PDT. OBJECTIVE: This study evaluates the effectiveness of PDT in the treatment of cSCC and BD for clearance rate (CR) after 1 year. METHODS: A literature search of studies of biopsy-proven BD and cSCC treated with PDT was performed. Pooled CRs were estimated. Subgroup analyses were performed based on follow-up, treatment regimen, lesion size, and site. RESULTS: Forty-three studies were included, enrolling 1943 BD lesions and 282 SCC lesions. Pooled CRs for BD and SCC were 76% (95% CI: 71%-80%; I2 = 78.9%) and 51% (95% CI: 35%-66%; I2 = 85.7%), respectively. CONCLUSION: Our findings support the selective use of PDT for BD; however, patients should be advised of potential for recurrence. Although PDT can be used for certain cases of cSCC, the high rate of treatment failure necessitates close surveillance for residual or recurrent disease. Further studies are needed to justify the usage of PDT in the treatment of BD and cSCC.

Immunocryosurgery is a safe and feasible treatment for basal cell carcinoma and Bowen disease in renal transplant recipients.

Keratinocyte skin carcinomas (squamous cell carcinoma, basal cell carcinoma [BCC], Bowen disease [BD]) inflict significant morbidity and constitute a treatment challenge in renal transplant recipients (RTR). Immunocryosurgery has shown efficacy >95% in the treatment of BCC and BD in immunocompetent patients. The present study evaluated the safety, feasibility and efficacy, of immunocryosurgery in the treatment of BCC and BD in a series of RTR. During a 3-year period, biopsy-confirmed cases of BCC and BD were treated with a standard immunocryosurgery cycle (5 weeks daily imiquimod and a session of cryosurgery at day 14). Safety was evaluated by comparing graft function markers between immunocryosurgery treated RTR patients and matched controls. Ten BCC (8 nodular, 1 basosquamous, 1 superficial; diameter 6-14 mm; mean 9.2 mm) and nine BD disease lesions in nine patients (7 men, 2 women; age range: 54-70 years, mean: 62.1 years) were treated with immunocryosurgery and followed-up for two to 5 years. Five BCC were located on the "H area" of the face. No patient showed clinical or laboratory signs of transplant dysfunction during treatment or follow-up. Seven out of 10 BCC lesions cleared completely after one 5-week immunocryosurgery cycle, two cleared after repeat and intensified treatment cycles and one responded only partially (clearance rate: 90%). Seven out of nine BD lesions cleared after one 5-week immunocryosurgery cycle and one lesion after two cycles (clearance rate: 88.9%). In conclusion, immunocryosurgery is a safe, feasible and effective minimally invasive treatment alternative to standard surgical modalities for BCC and BD in RTR.

Analysis and evaluation of the operational characteristics of a new photodynamic therapy device.

One of the key aspects of photodynamic therapy is the light source that is used to irradiate the lesion to be treated. The devices used must ensure that their emission spectrum matches the absorption spectrum of the photosensitizer, so that treatment radiation is delivered only on the target area, without irradiating healthy tissue at superficial or deep levels. Irradiance values must be adequate in order to avoid thermal damage, exceed the oxygen replenishment rate and avoid long treatment times. Furthermore, the device should be user-friendly, inexpensive, and able to be adapted to different photosensitizers. We have developed an easy-to-use and highly customizable device based on LED technology. Its innovative geometric design allows radiation to be delivered to a small treatment surface, since the LEDs are arranged in three arms, the configuration of which directs their radiation on the treatment point. Different high-power color LEDs are disposed on the arms, and can be independently selected based on the most effective wavelengths for exciting the different photodynamic therapy photosensitizers. We have tested the prototype in 5 different patients (1 actinic keratose, 1 actinic cheilitis, 1 superficial basal cell carcinoma and 2 Bowen's disease) and after 1-2 sessions of total cumulative dose of 25-50 J / cm2, 100% clearance of lesions were obtained. Our device can be used by any professional in the field, whether for medical or research purposes. It facilitates the development of treatment protocols and trials with different photosensitizers.

Efficacy of Photodynamic Therapy for the Treatment of Bowen's Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Photodynamic therapy is an established treatment option for Bowen's disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO2 laser or plum-blossom needle) for the treatment of Bowen's disease. METHODS: Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration's risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. RESULTS: Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], I2 = 86%, p = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], I2 = 0%, p = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], I2 = 0%, p = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO2 laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], I2 = 0%, p < 0.0001). Photodynamic therapy combined with ablative fractional CO2 laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], I2 = 0%, p = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], I2 = 0%, p = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO2 laser and photodynamic therapy combined with ablative fractional CO2 laser (RR = 1.00, 95% CI [0.54, 1.86], I2 not applicable, p = 1.00). CONCLUSIONS: This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen's disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO2 laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen's disease warrants further exploration.

Photodynamic therapy with light emitting fabrics: a review.

Photodynamic therapy is a powerful tool in the localized and selective treatment of dermatologic diseases, such as actinic keratosis, acne vulgaris, Bowen's disease and basal cell carcinoma. The success of photodynamic therapy is mainly attributed to the development of flexible light sources for homogenous and reproducible illumination during clinical studies. The essential requirement for this therapy includes, a suitable photosensitizer, presence of oxygen and a light of specific wavelength and intensity. The use of light emitting fabric comprising of optical fibers provides an exciting and an efficient way to transfer light directly to the skin uniformly on the infected body parts. As the optical fibers can transmit light from 400 to 1200 nm it is possible to combine light emitting fabric with laser sources for medical applications. This review focusses on the challenges and recent developments in the use of light emitting fabric for photodynamic therapy in clinical studies and its future perspectives.

Nanocarriers for Photodynamic Therapy Intended to Cutaneous Tumors.

Photodynamic Therapy (PDT) is a therapeutic modality used for several malignant and premalignant skin disorders, including Bowen's disease skin cancers and Superficial Basal Cell Carcinoma (BCC). Several photosensitizers (PSs) have been explored for tumor destruction of skin cancers, after their activation by a light source of appropriate wavelength. Topical release of PSs avoids prolonged photosensitization reactions associated with systemic administration; however, its clinical usefulness is influenced by its poor tissue penetration and the stability of the active agent. Nanotechnology-based drug delivery systems are promising tool to enhance the efficiency for PDT of cancer. This review focuses on PSs encapsulated in nanocarriers explored for PDT of skin tumors.

[Photodynamic therapy-trends and new developments]. / Photodynamische Therapie ­ Trends und neue Entwicklungen.

Photodynamic therapy (PDT) is a licensed and established procedure for the treatment of actinic keratosis, basal cell carcinoma, and Bowen's disease, but there are several new and clinically relevant developments and trends. These concern on the one hand the main components of PDT, which are the photosensitizer and the light source. Furthermore, modifications and therapy combinations have been developed that lead to an improved therapeutic efficacy. An important aspect of field-directed PDT is also skin cancer prevention. Finally, PDT has been used successfully for nonlicensed indications including inflammatory diseases and skin rejuvenation. This article focuses on these new developments and on recent guideline recommendations.

Efficacy of photodynamic therapy for the treatment of Bowen's disease: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This is a systematic review and meta-analysis on the effectiveness of Photodynamic Therapy (PDT) in Bowen's Disease (BD), with further summary of the data from all randomized controlled trials (RCTs). METHODS: Relevant data were extracted after conducting a literature search via PubMed, Embase, Scopus, the Cochrane Library, CNKI, and Wanfang databases, from inception until 31 July 2019. Meta-analyses of the data were performed using RevMan V.5.3. A total of 392 published RCTs related to the efficacy of PDT in BD treatment were identified. The papers were screened for duplicates and excluded based on title and abstract. Subsequently, 85 full-text articles were thoroughly reviewed and finally, data from 446 patients with 1147 skin lesions across 12 eligible studies were collated. RESULTS: Our findings revealed significant differences between the efficacies of PDT and other treatments, where a higher lesion reduction rate was observed after the first treatment session following PDT (P < 0.00001, Z = 4.98). PDT was found to be more effective than 5-fluorouracil (P < 0.00001, Z = 4.42) and cryotherapy (P = 0.008, Z = 2.67). However, there were no significant differences in recurrence rates following treatments with PDT, cryotherapy, and 5-fluorouracil. CONCLUSIONS: This systematic review and meta-analysis confirms and collates data from all RCTs pertaining to the efficacy of PDT for BD treatment. Our study has reiterated that PDT is more effective than 5-fluorouracil and cryotherapy for the treatment of BD.