Laser Assisted Drug Delivery in the Treatment of Superficial Non Melanoma Skin Cancer: a Randomized Controlled Trial

Superficial Basal Cell Carcinoma (sBCC) and Bowen Disease (BD) are malignant skin tumors localised in the superficial epidermis. These tumors are highly prevalent in the caucasian population. Diagnosis of sBCC and BD is often delayed because the clinical manifestation may be discrete and lesions are sometimes wrongly diagnosed and treated as eczema. Once the diagnosis is established, the lesions may cover an extensive area, making surgical excision more difficult. At that moment, the physician can make use of less invasive techniques such as photodynamic therapy (PDT). Pretreatment with an ablative carbon dioxide (CO2) laser has recently been studied in order to enhance the skin penetration of the photosensitizer methyl aminolevulinate (MAL). This study compares the results of a full ablative and a fractional ablative CO2 laser mode as pretreatment of PDT in the management of sBCC and BD. Ablation of the upper epiderm of the cancer results in an deeper penetration of MAL. Fractional ablation is known to result in better wound healing compared to full ablative CO2 laser ablation, because only small skin columns are ablated instead of the entire epidermal layer. Patients with non operable sBCC or BD lesions covering an area of at least 5 cm2 or with the presence of two small separated lesions, will be investigated. Lesions greater than 5 cm2 are divided in two. After randomization, the half of the lesions will be pretreated with the full ablative CO2 laser, while the other half with the fractional ablative CO2 laser. Afterwards, the entire surface is treated with MAL-PDT. Such as in our current clinical practice, this treatment modality is repeated after a two week interval. Thus, every subject undergoes both treatment modalities, making within-patient comparison possible. The endpoints efficacy, pain, aesthetics and patient preference are investigated during twelve months of follow up.

• full ablative CO2 laser (Device), also known as full ablative carbon dioxide laser: ablation to the level of de dermal papilla
• fractional ablative CO2 laser (Device), also known as fractional ablative carbon dioxide laser: 180 micron HP, pulse 8ms, 15% overlay, 30 W (943J/cm)
• MAL (Drug), also known as methyl aminolevulinate, Metvix® (Galderma)
• LED lamp (Device), also known as Aktilite® (Galderma), light-emitting diodes: peak wavelength 630 nm, 37J/cm2
• lidocaine hydrochloride 2% with epinephrine (Drug), also known as local anaesthetic, xylocaine® 2% with epinephrine

Primary outcomes

• Clinical efficacy after twelve months of follow up [month 12]: A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression.

Secondary outcomes

• Clinical efficacy after six months of follow up [month 6]: A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression.
• Clinical efficacy after three months of follow up [month 3]: A three point scale with complete regression (CR), partial regression (PR) and no regression (NR) defined respectively as 100%, 25-99% and 0-25% regression.
• Histological efficacy after twelve months of follow up [month 12]
• Pain during the first treatment session [immediately after the first treatment session (day 1)]: The experienced pain during the treatment is scored bye the patient using a VAS scale of 100 mm.
• Pain during the second treatment session [immediately after the second treatment session (day 14)]: The experienced pain during the treatment is scored by the patient using a VAS scale of 100 mm.
• Side effects after the first treatment session [immediately after the first treatment session (day 1)]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after one week of follow up, telephone survey [day 7]: The presence of following side effects is evaluated by the patient: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects before the second treatment session [before initiation of the second treatment session (day 14)]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after the second treatment [immediately after the second treatment session (day 14)]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after two weeks of follow up, telephone survey [day 21]: The presence of following side effects is evaluated by the patient: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after three months follow up [month 3]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after six months of follow up [month 6]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Side effects after twelve months of follow up [month 12]: The presence of following side effects is evaluated by the investigator: erythema, vesicles, pigment changes, scarring, infection and pain.
• Aesthetic result after three months of follow up [month 3]: The aesthetic result is scored by a blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Aesthetic result after six months of follow up [month 6]: The aesthetic result is scored a by blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Aesthetic result after twelve months of follow up [month 12]: The aesthetic result is scored a by blinded investigator using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Aesthetic result according to the patient after three months of follow up [month 3]: The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Aesthetic result according to the patient after six months of follow up [month 6]: The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Aesthetic result according to the patient after twelve months of follow up [month 12]: The aesthetic result is scored by the patient using a four point scale: excellent (no significant changes), good (minor changes), poor (serious dyspigmentation, visible scarring), very poor (important scarring).
• Technique of preference according to the patient [month 12]: Patients are asked for their preferred therapy. Following options exist: (1) full ablative CO2 laser + PDT, (2) fractional ablative CO2 laser + PDT, (3) no preference

Sex: All, ages: 18 Years to any

Inclusion Criteria: patients with the presence of

* non operable superficial Basal Cell Carcinoma or Bowen's Disease lesions
* and the presence of at least two lesions or the presence of one lesion covering an area greater than 5cm2

Exclusion Criteria: pregnancy and/or breast feeding

• Barbara Boone, MD PhD, Principal investigator, Ghent University, Dpt. of Dermatology