Ernest Allan

Efficacy of Photodynamic Therapy as a Treatment for Gorlin Syndrome-related Basal Cell Carcinomas

AIMS The management of the multiple basal cell carcinomas (BCCs) that develop throughout life of patients with Gorlin syndrome can be challenging. Surgical excision can result in significant disfigurement from scarring and tissue defects. Radiotherapy is contraindicated because of enhanced radiation tumourigenesis in these patients. Photodynamic therapy (PDT) is a simple, repeatable out-patient procedure, which is associated with minimal skin deterioration. It is now routinely used to treat superficial sporadic BCCs, using a topically-applied photosensitiser and external light, but its role in the management of Gorlin syndrome-related BCCs has yet to be established. In particular, Gorlin syndrome is often associated thick, nodular lesions which can be resistant to treatment with topical PDT. MATERIALS AND METHODS We report our outcome data for 33 Gorlin patients (138 lesions) treated with PDT. Lesion thicknesses were assessed using ultrasound, both prior to treatment and during follow-up, to quantify treatment response and to guide the choice of treatment methods. Topical PDT was used to treat superficial lesions (<2 mm thick) and a systemic photosensitiser +/- light delivered by interstitially-placed optical fibres was employed for thicker lesions (>2 mm). RESULTS AND CONCLUSIONS Local control rates of 56.3% at 12 months were achieved overall. The use of a systemic photosensitiser +/- interstitial light delivery extended the remit of PDT, allowing thicker lesions (>2 mm) to be treated, resulting in local control rates of 59.3% in this group. PDT can be considered as a treatment option for patients with multiple BCCs as a result of Gorlin syndrome. The use of ultrasound to accurately assess lesion thickness helps to select the optimum treatment method. Systemic photosensitisers and interstitial optical fibres can be used to treat thicker lesions, offering a treatment option for patients with thick nodular tumours who wish to avoid surgery.

Hand Function after High Dose Rate Brachytherapy for Squamous Cell Carcinoma of the Skin of the Hand

AIMS Current recommendations for the treatment of squamous cell carcinoma of the hand are almost unanimously in favour of ablative surgery. However, many of the patients are frail and elderly, and surgical techniques frequently involve skin grafts or amputation of digits. A non-invasive method of treatment is, therefore, often preferred. Radiotherapy using a brachytherapy technique is a well-established option. This study investigated whether patients found the treatment acceptable and assessed the outcome of treatment in terms of local control, cosmesis and hand function. MATERIALS AND METHODS Twenty-five patients who underwent mould brachytherapy using a microselectron high dose rate radiotherapy device were available for assessment. We assessed the functional status of the hand and fingers by means of the Disability of Arm, Shoulder and Hand and Michigan Hand Outcomes questionnaires. We examined the hand to assess the severity of post-radiation stigmata. We enquired as to patient acceptability of treatment and outcome. RESULTS Of 25 patients who agreed to participate, the fingers were affected in 15 and the dorsum of the hand in 10. The mean age at the time of radiotherapy was 69 years (range 50-87). There were no significant differences in parameters, such as range of motion of fingers and wrist, hand/finger grip strength, between the treated and opposite sides. Sensation, including two-point discrimination, was not significantly different from the untreated hand. Seventeen patients had minor skin changes. No patient found the treatment painful or unacceptable. Twenty patients were very satisfied and five patients were moderately satisfied with the cosmetic result. CONCLUSIONS We conclude that high dose rate brachytherapy is a safe and simple alternative to surgical treatment for squamous cell carcinoma of the hand, as it is not only successful in eradicating tumour, but also preserves hand function.

Addition of novel degenerate electrical waveform stimulation with photodynamic therapy significantly enhances its cytotoxic effect in keloid fibroblasts: first report of a potential combination therapy.

BACKGROUND We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. OBJECTIVE In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm(2) and 10J/cm(2) of red light (633 ± 3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. METHODS The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. RESULTS PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT+DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT+DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT+DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). CONCLUSION The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy.

Systemic photodynamic therapy with Photofrin for naevoid basal cell carcinoma syndrome—A pilot study

BACKGROUND Treatment of basal cell carcinomas in naevoid basal cell carcinoma syndrome (NBCCS) poses several challenges. The sheer numbers of such lesions in these patients makes traditional therapeutic modalities like surgery, impractical. Topical photodynamic therapy (PDT) with δ-5-amino levulinic acid has increasingly been recognised as and safe and effective choice in the treatment of BCC. The probability of local control of BCC treated by PDT depends strongly on lesion thickness, thick nodular lesions being less responsive. Response to treatment is monitored by the reduction in the lesional size, but histopathological confirmation of regression is often required. METHOD We used systemic photodynamic therapy with Porfimer Sodium (Photofrin(®), Axcan Pharma Inc., Quebec, Canada), a systemic photosensitizer for treating multiple BCC in seven patients with NBCCS. Treatment response was monitored using a high resolution 20MHz ultrasound. RESULTS There was a substantial reduction in the number of superficial basal cell carcinomas with complete US regression after one treatment. A 74.2% reduction was seen in the size of thick lesions treated with external light. Thick nodular lesions in two patients treated with interstitial optical diffuser fibres in addition to external light showed 87.6% reduction in size as measured by high resolution ultrasound. CONCLUSIONS Our preliminary results indicate that systemic photodynamic therapy using Photofrin and external light either alone or with interstitial optical diffuser fibres; may be effective in treatment of multiple, thick and nodular BCC lesions in Naevoid basal cell carcinoma syndrome. Further studies are needed to confirm our observations. We found high resolution ultrasound an effective alternative to histopathological analysis in monitoring the response to treatment.

An ultrasound analysis of the response of Gorlin syndrome-related and sporadic basal cell carcinomas to aminolaevulinic acid photodynamic therapy

BACKGROUND Gorlin Syndrome (naevoid basal cell carcinoma syndrome, NBCCS) predisposes the patient to the development of basal cell carcinomas (BCCs) throughout their life. The standard treatment for isolated lesions is surgical excision. However, when numerous surgical procedures are required over time, the patient can be left with multiple disfiguring scars. Photodynamic therapy (PDT) offers a non-invasive treatment option for patients with this condition, in which ionizing radiation is contraindicated. This study evaluates PDT as a treatment modality for Gorlin Syndrome and compares the treatment response of Gorlin-related basal cell carcinomas with that of the sporadic lesions. METHODS In this un-randomized study, basal cell carcinomas in 25 Gorlin syndrome patients (with 36 lesions) and 145 sporadic patients (with 189 lesions) were treated by photodynamic therapy, using δ-5-aminolaevulinic acid (ALA) as a photosensitizer and 100Jcm(-2) of red light (630±15nm). The maximum thickness of the BCC was measured by 20MHz pulsed ultrasound prior to treatment and again 4-6 weeks and 12 months following treatment. The response of Gorlin syndrome lesions was compared to those in the overall sporadic population and then to a subpopulation matched as closely as possible for age, lesion thickness and site. RESULTS For both populations, the average pre-treatment BCC thickness by US was 1.5mm (overall range 0.3-5.3), and the average thickness at 4-6 weeks post-treatment was 0.5mm (overall range 0-4.3). Those BCC less than 1.5mm thick prior to treatment were significantly more likely to have no US evidence of disease at 4-6 weeks than and were more likely to be controlled at 12 months. CONCLUSIONS The average response to ALA PDT of Gorlin syndrome-related BCC closely resembles that for the sporadic population, with the same wide range of responses for a given dose. Ultrasound parameters measured at treatment and at 4-6 weeks post-treatment aid prediction of outcome and necessity for further treatment.

Systemic photodynamic therapy in folliculitis decalvans.

Folliculitis decalvans (FD) is classified as a primary neutrophilic cicatricial alopecia, and is estimated to account for approximately 10% of all cases of primary cicatricial alopecia. The role of dysfunctional immune activity and the presence of bacteria, particularly Staphylococcus aureus, appear pivotal. We describe a 26‐year‐old man with a 4‐year history of FD that was recalcitrant to numerous systemic and topical therapies, whose disease was virtually cleared during a follow‐up of 25 months following a course of treatment with systemic photodynamic therapy (PDT) using ultraviolet light (100–140 J/cm2) with porfimer sodium 1 mg/kg as monotherapy. This is the first report of the use of systemic PDT as a treatment for FD. Systemic PDT has potent antibacterial effects with little or no resistance. In addition, systemic PDT provides local immunomodulation and improved scar healing. Significant adverse effects following systemic PDT with appropriate aftercare are rare. This case demonstrates that systemic PDT is a useful therapy option in the treatment of recalcitrant FD.

Taking cutaneous PDT to the next level.

c i t p c i r Sally Ibbotson and Alexis Sidoroff are to be congratulated on their clear and concise accounts of the place of Photodynamic Therapy (PDT) in the treatment of cutaneous pathology. Many dermatologists present patients with a list of possible treatments and ask them to make a choice. Sally Ibbotson and Alexis Sidoroff both forcibly make the point that the treatments are not interchangeable and that there are specific indications for each treatment although there is inevitably some overlap. These papers provide the clinician with sufficient understanding of the issues involved to confidently advise his patient of the optimum treatment for his condition. Many patients research the internet to find a treatment that inflicts as little trauma as possible and produces the best possible cosmetic outcome. Sally Ibbotson and Alexis Sidoroff have provided a valuable service to clinicians in that they will have a greater knowledge to advise patients whether PDT is a suitable option for them. There are however two issues that give cause for some disquiet: