mutations, some of these actinic keratosis lesions may progress to SCC. Topical 0.5% ... Histological evidence of AKs and solar elastosis are often apparent at.
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TOPICAL 0.5% FLUOROURACIL TREATMENT FOLLOWING MOHS’ SURGERY FOR SQUAMOUS CELL CARCINOMA FOR THE PREVENTION OF FUTURE SQUAMOUS CELL CARCINOMA Perry Robins, MD, NYU Medical Center, New York, NY, United States, Elizabeth Hale, MD, NYU Medical Center, New York, NY, United States Squamous cell carcinoma (SCC) occurs most commonly in patients with extensive actinic damage and often occurs in sun-exposed skin areas. This form of skin cancer typically follows a spectrum of events beginning with the development of sun-damaged keratinocytes that have the potential to develop into actinic keratoses (AKs), which are commonly referred to as precursor lesions to SCC. With continued sun damage and acquired mutations, some of these actinic keratosis lesions may progress to SCC. Topical 0.5% fluorouracil is commonly used for the treatment of patients with actinic keratosis. It is highly likely that actinic keratoses and sun-damaged keratinocytes are present in the skin surrounding a SCC. Histological evidence of AKs and solar elastosis are often apparent at the margins of frozen tissue sections obtained during Mohs’ surgery for SCC. Therefore, it is proposed that treatment with topical 0.5% fluorouracil following Mohs’ surgery may diminish the future development of SCC in the same area by eradicating both clinical and subclinical actinic keratosis lesions. The objective of this pilot study is to determine if administration of topical 0.5% fluorouracil cream following Mohs’ surgery for SCC diminishes the occurrence of future SCC cases in the same area. A total of 5-10 patients undergoing Moh’s surgery for SCC will be enrolled and treated. After complete excision with frozen microscopic control, patients will apply topical 0.5% fluorouracil once daily for 3 weeks. Clinical improvement of the surrounding skin will be evaluated following treatment. Adverse events will be followed continuously through self-reporting and active questioning during all visits. Final data will be presented.
IMPACT OF NEW IMMUNOSUPPRESSANTS ON THE DERMATOLOGICAL OUTCOME OF ORGAN TRANSPLANT PATIENTS Claas Ulrich, MD, Dept Dermatology, Charite´, Berlin, 10117 Berlin, Germany, Sylvie Euvrard, MD, Hospital Edouard Herriot, Lyon, France, Stuart Salasche, MD, University of Arizona Health Sciences Center, AZ, United States, Tobias Schmook, MD, Dept Dermatology, Charite´, Berlin, 10117 Berlin, Germany Background: Skin infections and the increased risk for non-melanoma skin cancer (NMSC) represent a key problem in the long term maintenance of organ transplant patients. The responsibility of immunosuppressive treatments in the increased risk of skin cancer is widely recognized and a decreased of tumors after reduction or cessation of treatments has been described. However especially in patients with already minimized immunosuppressive levels a further lowering of the immunosuppression might induce graft rejection. Recent discussions therefore focus on combination or substitution of traditional drugs with new immunosuppressants related to a more specific immunosuppression. Nevertheless only large networks could epidemiologically cover the amount of patients with different immunosuppressive regimens required for a precise analysis of the actual impact of individual immunosuppressants. Methods: In 2001 the European Skin Care in Organ Transplant Collaborative Network together with the US partner organization International Transplant-Skin Cancer Collaborative (ITSCC) established a computerized database to collect epidemiological information skin diseases and risk factors including immunosuppressive regimens. Meanwhile the cases of over 700 patients are documented and data analysis are constantly performed. Results: Among patients on calcineurin inhibitors those treated with non TGF-beta inducing potential benefited from a slightly lower skin cancer incidence. Combination therapies with mycophenolate mofetil (MMF) allows to lower the level of calcineurin inhibitor dosages and in direct comparison with azathioprine MMF treated patients showed a significant lower skin cancer incidence. New immunosuppressive drugs like the mTOR inhibitor rapamycin and everolimus showed a lower incidence of skin malignancy in all groups of patients treated with rapamycin related regimens. Conclusions: Analysis of raised data on skin diseases and their relation to different immunosuppressive regiments may help transplant surgeons to improve the quality of long term immunosuppressive therapies and might also have an impact on dermatological therapies applied for chronic autoimmune disorders.
Disclosure not available at press time. Medical writing supported by Dermik Laboratories.
Disclosure not available at press time.
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SKIN CANCER RISK ASSESSMENT Anthony D Peterson, MD, Loyola University Chicago, Maywood, IL, United States, Heather Downes, BS, Loyola University Chicago, Maywood, IL, United States, June Robinson, MD, Loyola University Chicago, Maywood, IL, United States Background: Improving skin cancer risk perception may enhance primary and secondary prevention of skin cancer. Objective: To develop reliable measures, which are easy to use for both individuals who may be at risk and health care workers, assessing skin cancer risk by evaluating the skin type, environmental exposure to ultraviolet radiation, and evidence of photodamage. Methods: Fifty people with a history of skin cancer and their family members provided responses to questions that assessed the Fitzpatrick skin type, and the total sun burden score. The total sun burden scoring system was developed in 1999 by Espana et al. to quantify the total sun burden of an individual. This score was based on a points system summed from four periods of an individual’s life (⬍20y, 20-40y, 41-60y, ⬎60y). Test, re-test for reliability was repeated after a two week interval. Two physicians independently evaluated photodamage on the forearm of subjects with no sun exposure during this time and repeated it in 6 weeks. Actinic keratoses, pigmentary change, wrinkles, atrophy, telangiectasia, and tenting were quantitatively graded with the first three as: (none ⫽ 0, mild ⫽ 1, moderate ⫽ 2, severe ⫽ 3), the last three as: (present ⫽ 1, absent ⫽ 0). Results: The Fitzpatrick skin type assessment and Total Sun Burden Score were reliable. Photodamage features with interobserver reliability were actinic keratosis, telangiectasia, pigmentary change, and atrophy. Conclusion: Many environmental risk assessments, which are self-reported from the patient’s memory, are highly subjective. Our adaptation of the Sun Burden Score removes the subjectivity from the person’s report of the amount of sun at their residence. Using the ultraviolet index, a numerical value was assigned to the location of residence to quantify an individual’s UV exposure. Also, the total sun burden score was adjusted to compare occupational sun exposure to exposure associated with vacation for those residing in North America. A weighting scale relates each photoaging criteria to the skin cancer risk with actinic keratoses having the greatest weight. The Fitzpatrick skin type and total sun burden scores may become self-administered tests. The photodamage assessment can be learned by non-dermatologists when the skills training is learned in a structured mentorship under standardized conditions. Future study will determine if these tools enhance risk perception.
EFFICACY OF TOPICAL ANTIANGIOGENIC THERAPY FOR BASAL CELL AND SQUAMOUS CELL CARCINOMA: A CASE SERIES OF 123 LESIONS Sarvenaz Zand, Harvard Medical School, Cambridge, MA, United States, William W. Li, MD, Institute for Advanced Studies, The Angiogenesis Foundation, Cambridge, MA, United States, Vincent W. Li, MD, MBA, Institute for Advanced Studies, The Angiogenesis Foundation, Cambridge, MA, United States Background: Approximately 1.3 million people in the U.S. are diagnosed annually with nonmelanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In cases of extensive disease or severe comorbidities, conventional treatment modalities such as surgical excision, cryotherapy, or electrodessication and curretage may be impractical, physically disfiguring, technically unfeasible, and may impair quality of life. Because angiogenesis is known to be a critical event in malignant transformation in skin cancer, we sought to utilize a topical antiangiogenic approach in treating this patient population. Methods: We devised a topical antiangiogenic regimen (OLCAT-005) for BCC, SCC in situ, and invasive SCC based on a multi-targeting combinatorial approach utilizing FDAapproved drugs. The regimen included imiquimod, tretinoin, calcipotriene, diclofenac, and hydrocortisone valerate in a 1:1:1:1:1 ratio. Each drug targets specific antiangiogenic mechanisms, including interferons, IL-12, RAR-alpha, endothelial apoptosis, COX-2 mediated VEGF production, and basement membrane disruption. Patients who were unable to undergo or refused conventional treatment modalities were treated on an individual basis using OLCAT-005. Frequency of administration was determined by an Individualized Maximally Tolerated Dose (IMTD) algorithm. Results: A total of 123 lesions (30 SCC, 19 SCCIS, 74 BCC) on 19 patients were treated from 1998-2003. Pathological confirmation of initial diagnosis and clinical response was obtained in 18/19 and 15/19 patients, respectively. We found complete (100%) response with clinical and pathological clearance after 10-15 (mean ⫽ 12) weeks of treatment. Patient follow-up ranged from 1-42 months (mean ⫽ 23), during which no (0%) recurrence was observed. Using the IMTD algorithm, OLCAT-005 was well-tolerated, with erythema as the most frequent reaction. Excellent cosmetic outcome was achieved without contour irregularity, atrophy, hypertrophic scar, or depigmentation. Summary: We report the successful use of topical combination antiangiogenic therapy (OLCAT-005) for BCC, SCC in situ, and invasive SCC in patients unable to undergo or refusing conventional treatment modalities. Complete responses were achieved with no recurrence. Further studies are ongoing.
Disclosure not available at press time.
Disclosure not available at press time.
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J AM ACAD DERMATOL
MARCH 2004
