European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications – actinic keratoses,Bowen’s disease,basal cell carcinoma

Topical photodynamic therapy (PDT) is a widely used non‐invasive treatment for certain non‐melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non‐hyperkeratotic actinic keratoses, Bowen’s disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain‐minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.     

European Dermatology Forum guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.     

Bowen's disease, solar keratoses and superficial basal cell carcinomas treated by photodynamic therapy using a large-field incoherent light source

BACKGROUND: Photodynamic therapy (PDT) has not yet been demonstrated to be superior to conventional treatment in the treatment of superficial skin cancers and premalignant skin conditions. A limitation for PDT is the absence to date of a light source suitable for the treatment of larger lesions or 'field changes' where several lesions are present on one anatomical site. OBJECTIVES: To investigate the safety and efficacy of a large field light source, the Waldmann PDT 1200, in the treatment of Bowen's disease (BD), superficial basal cell carcinomas (BCCs) and solar keratoses (SKs). METHODS: After application of 5-aminolaevulinic acid for 4-6 h, each lesion was irradiated with 105 J cm-2 of incoherent red light centred on 640 nm. Eighty-eight patients with 239 lesions were recruited. RESULTS: Within two treatments, 88% of BD lesions, 95% of BCCs and 99% of SKs showed complete clinical clearance. At 12 months the complete response rates were 69% for BD, 82% for BCC and 72% for SK. CONCLUSIONS: This study confirms that PDT is a useful treatment and that selected superficial BCCs and SKs respond well to PDT. The PDT 1200 light source proved capable of treating multiple lesions amounting to a 'field change' and also lesions up to 10 cm in diameter within an acceptable treatment time. Thus far, PDT has failed to become established as a routine treatment for small premalignant and malignant skin lesions as it has not proved superior to simple cheaper conventional therapies such as cryotherapy, curettage and cautery, topical chemotherapy with 5-fluorouracil, or surgery. However, PDT has become established as a treatment for selected cases in some centres. This study suggests a role for PDT in the treatment of large premalignancies, superficial BCCs and field change where existing treatments may be problematic.     

In vivo fluorescence kinetics and photodynamic therapy efficacy of delta-aminolevulinic acid-induced porphyrins in basal cell carcinomas and actinic keratoses; implications for optimization of photodynamic therapy

Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a therapeutic option of growing interest for superficial non-melanoma precancerous and malignant lesions. After application of ALA, in situ conversion to endogenous porphyrins is accomplished in a gradual manner. Therefore, the determination of fluorescence kinetics and spatial distribution in vivo versus time is a crucial point for the success of ALA-PDT. Seventeen basal cell carcinomas (BCC) and 20 actinic keratoses (AK) were enrolled in this study. In 5 BCC and 4 AK, in vivo fluorescence kinetics were performed over 24 hrs and for the remaining lesions between 2 and 7 hrs after ALA application. In vivo spatial and quantitative detection of the fluorescence intensity versus time showed considerable variations among tumors of the same type, so light irradiation was performed according to patient individualities. Both BCC and AK showed maximal median fluorescence intensity at 4-6.5 hrs post-application. In the present study, a high cure rate was proven after topical ALA-PDT (70.6% in BCC and 85% in AK). The results of fluorescence studies suggest that optimum irradiation time for BCC is approximately 3.5-5 hrs and for AK 5 hrs after ALA application, when relative maximal fluorescence intensity in correlation with fluorescence selectivity on the lesion, is obtained.     

European guidelines for topical photodynamic therapy part 2: emerging indications – field cancerization,photorejuvenation and inflammatory/infective dermatoses

In addition to established indications in non‐melanoma skin cancer in immunocompetent patients, photodynamic therapy (PDT) has been studied for the treatment, and possible prevention, of superficial skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photodamaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. PDT has been studied in patch/plaque‐stage cutaneous T‐cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. Despite proven efficacy, PDT is not widely used in viral/genital warts, where pain during treatment can be intense. PDT is a therapeutic option for photorejuvenation, with improvement in fine wrinkles, mottled hyperpigmentation, roughness and sallowness reported.     

Photodynamic therapy with violet light and topical δ-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinoma

BACKGROUND: Most clinical studies using photodynamic therapy (PDT) with topical application of delta-aminolaevulinic acid (delta-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of delta-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. AIM: To study the efficacy of violet light in combination with topical delta-ALA PDT in the treatment of pre-malignant and malignant skin lesions. METHODS: Eight hours after 20% delta-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400-450 nm). Lesions received 10-20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. RESULTS: Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90-100% of the solitary lesions of Bowen's disease. CONCLUSIONS: delta-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin.     

Therapeutic modalities and economic assessment in the treatment of superficial basal cell carcinomas and multiple actinic keratoses by French dermatologists

INTRODUCTION: To date, no prospective studies have been conducted in France describing the management of actinic keratoses (AK) and superficial basal cell carcinomas (sBCC). The aim of the present study was to describe the therapeutic modalities for AK and sBCC adopted by French dermatologists and to determine the direct annual medical costs. PATIENTS AND METHODS: This was a prospective, observational study conducted in France between January and June 2004 in a random selection of representative dermatologists (n=202). The first 5 adult patients seen for one or more sBCCs and the first patient with at least 4 AKs over a period of four non-consecutive weeks were included in the study. The following data were recorded using a standardized questionnaire at inclusion: date of birth, gender, habitat, professional activity, social insurance regimen, site, number and maximum size of lesions. The therapeutic modalities, the physicians involved and the laboratory examinations during the 3 months following diagnosis were recorded prospectively. Medical management costs were calculated taking into account the usual parameters (e.g. French nomenclature of medical acts). RESULTS: 512 patients with sBCC (mean age: 69 years; sex-ratio M/F: 0.92) were included in the study. sBCC was isolated in 80% of cases, measured less than 2 cm in 90%, and was located on the head/neck in 51% and on the trunk in 37%. Histological confirmation of diagnosis of BCC was obtained in 85% of cases. Treatment comprised surgical excision in 70% of cases, cryotherapy in 13%, topical therapy in 7% and curettage/electrodessication in 4%. Clinical follow-up was performed in 79% of cases. The mean cost per patient over 3 months was 139 euros (CI95%: 125-153). In addition, 226 patients with AK (mean age: 76 years; sex-ratio M/F: 2.1) were included in the study. AKs were located on the head/neck in 74% of cases and on the trunk in 6%. Treatment consisted of cryotherapy in 92% of cases. The mean cost per patient over 3 months was calculated at 85 euros (CI95%: 71-99). An on-site audit of 5% of the investigators gave a concordance rate of 98.8%. DISCUSSION: This is the first study conducted in France to evaluate both the medical approach and treatment costs of sBCC and AK. Finally, the mostly surgical treatment of sBCC observed is in accordance with the recent French ANAES guidelines. When extrapolating the results of the present study, the annual cost of treatment of sBCC by French dermatologists may be estimated at between 10.2 and 10.6m euros.     

Multiple familial and pigmented basal cell carcinomas in early childhood – Bazex–Dupré–Christol syndrome

Background Bazex–Dupré–Christol syndrome (BDCS) is an X‐linked dominantly inherited disorder affecting hair follicle structures. Currently, hypotrichosis, follicular atrophoderma and basal cell carcinomas are considered frequent symptoms of the disorder whereas milia are supposed to reflect infrequent clinical signs. Usually, basal cell carcinomas in this disease manifest from the second decade of life onwards. Case report Here, we studied a novel multigeneration family of German origin with BDCS. Interestingly, two family members developed pigmented basal cell carcinomas in early childhood, at the age of 3 and 5 years, respectively. The differentiation from other pigmented lesions was accomplished by both dermoscopy and histopathology. A thorough survey of the current literature revealed that milia were present in almost all patients with BDCS reported, as is the case in our family. Conclusions We suggest that milia should also be considered frequent symptoms in BDCS. For the first time, to the best of our knowledge, we describe the occurrence of pigmented basal cell carcinomas in BDCS during the first decade of life. Our observation emphasizes the importance of screening for cutaneous malignancies in this disorder already at young age.