Photodynamic therapy for prevention of skin cancers

A prospective multicentre multinational randomized controlled trial is planned. The control group will be managed by observation, review with surgical management of future skin cancers if and when they occur. The observation group reflects current common practice. That is, current practice is that patients who have had skin cancers are followed through indefinitely to observe for new skin cancers to be then treated once they are diagnosed. The intervention group will have pre-treatment with AHA followed by PDT. Intervention centres: This trial will take place at 6 centres managing patients with skin cancer and actinic keratoses. There will be 6 centres in Australia, Victoria X 2, Western Australia, New South Wales and Queensland X 2 sites. These sites provide a combination of northern, central and southern latitudes as well as eastern and western longitudes. There will also be a northern hemisphere centre based in Missouri USA. Each treatment centre will be provided with the required products and illumination light. Intervention arm: Patients randomized to the intervention arm will be supplied with “Face Repair” (Allmedic ® 10% alpha hydroxy acid solution) to use twice daily for 14 days prior to the initial PDT treatment. They will also be provided with a SPF 30 antioxidant sunscreen (Allmedic ®) for usage twice daily in the lead up to PDT. Two PDT treatments will be effected 10 to 14 days apart. The patient will be incubated with Allmedic ® 20% ALA to each side of the face. Incubation will involve the liquid being massaged into each side of face to provide a thin and uniform cover. Incubation will be effected by the doctor or practice nurse. All such medical staff will be trained in advance regarding this technique. A firm massage of the liquid into the face will be effected. No product will be applied close to eye lashes or pink lip. Otherwise all skin areas from the hairline to the lower border of the mandible and from anterior border of the ear to the opposite anterior border of the ear will be included. There will be 5 hours planned between incubation and illumination. During this period, the patient will be advised to wear a broad brimmed hat and to avoid sunlight or bright lights. The patient will be encouraged to remain indoors whenever possible between incubation and illumination. Prior to illumination, the face will be washed with warm water and dried. During illumination, the eyes of the patient will be shielded from the light source. Each patient will have an attendant(s) at all times during illumination. A fan to reduce heat of treatment will be provided as required. The attendant(s) will wear dark sun glasses during illumination. Illumination will involve the Allmedic ® Tru+PDT light source, applied with the blue light for 20 minutes and then the red light for 10 minutes. No ultraviolet light will be used in the illumination phase. Following treatment, the patient will be advised to continue to wear the broad brimmed hat indoors and outdoors for five days and to continue to avoid bright lights. Advice re analgesia and moisturising cream will be provided. A second PDT treatment 10 to 14 days later will follow the same process. Observation arm: No immediate treatment or intervention will be provided for their background sun damaged skin. They will be followed up as detailed below. All patients, (including observation patients) will be given general advice regarding sun protection including sunscreens when outdoors. It is recognised that even sunscreens can have an effect on reducing actinic keratoses.31, 32 Follow up: All patients will have scheduled appointments each six months for two years following randomization. Patients will be further invited to attend for appointments in addition to scheduled appointments if they consider problems have arisen or occurring requiring such attention. At follow up, any face lesion suspicious of skin malignancy will be punch biopsied or locally excised. The punch biopsy will be a minimum of 4 mm in diameter. Where histology demonstrates actinic damage but no skin cancer (as previously defined), the lesion will be observed. Where the histology indicates skin cancer, treatment will be by surgical excision. This may involve Mohs’ surgery if considered appropriate. New face skin cancers occurring during the follow up two year period will not be treated with imiquimod, 5FU, curettage, ablation, etc,. At each follow up appointment, a further on line progress form will be downloaded to the central study database. The doctor and patient will both compare their face at each appointment to the baseline enrolment photograph. If a lesion is biopsied and / or excised on the face in that two year period, a further form will be completed on line and downloaded detailing such an event. Photography: Each enrolled patient will be photographed prior to any intervention. The digital photograph will be taken with the camera at least 1.5 metres from the patient. A minimum 6 Megapixel digital camera image will be taken and stored. The photograph will involve only the face from the neck up. The subject will be facing directly towards and looking at the camera. Controlled lighting and conditions will apply. At 6 months post randomization and at completion of follow up, photographs of the same methodology will be taken. Photographs will be used to assist patients and clinicians detecting an appearance alteration during the trial period.