252 Chemoprevention of basal and squamous cell carcinoma with a single course of 5-flourouracil 5% cream

Abstract

252 Chemoprevention of basal and squamous cell carcinoma with a single course of 5-flourouracil 5% cream MAWeinstock, K Marcolivio and S Thwin, V Trial Group 1 VA Med Ctr, Providence, RI, 2 Brown Univ, Providence, RI and 3 VA Healthcare Syst, Boston, MA Keratinocyte carcinoma (KC; basal cell and squamous cell carcinoma of the skin, i.e. BCC and SCC) is the most common cancer in the United States and throughout the world’s lightskinned population, with over 5 million cases per year in the US alone, and its incidence is increasing. Topical 5% 5-fluorouracil (5-FU) has been used for decades for the treatment of actinic keratosis, a known precursor of SCC. We sought to test whether topical application of 5-FU could be an effective regimen for the prevention of BCC and SCC of the face and ears that require surgery. We recruited a high-risk population of 932 veterans at 12 Veterans Affairs Medical Centers who had a history of at least 2 KCs during the prior 5 years, at least one of which was on the face or ears. They were randomized to apply a standard course of 28 to 56 applications (twice daily for 2 to 4 weeks) of 5-FU 5% cream or vehicle control cream to the face and ears. Investigators were blinded to randomization group and did not examine study participants during the first 6 months after initiating application of the study cream. All lesions biopsied from the face or ears were reviewed by a board-certified study dermatopathologist who was blinded to group assignment. During this 4 year trial (median follow-up 2.6 years), 299 participants developed a BCC on the face or ears requiring surgery and 108 developed an SCC that met the same criteria. Over the 4 year trial period, there was no difference in risk of KC, BCC, or SCC. However, during the first year of follow-up, there was a 74% reduction in SCCs requiring surgery in the 5-FU group compared to vehicle control (HR1⁄40.25, 95% CI 0.09-0.68, p1⁄40.003), whereas there was no difference in BCC or overall KC. These data demonstrate that a conventional course of 5-FU to the face and ears substantially reduces surgery for SCC on the face and ears for at least 1 year without affecting the corresponding risk for BCC. 253 Sirolimus for the treatment of venolymphatic and lymphatic malformations in children: A volumetric analysis JH Tu, HI Cohn, HM Do, K Yeom, A Marqueling, M Sofilos, M Jeng and J Teng 1 Vascular Anomalies Clinic, Stanford University, Stanford, CA, 2 Columbia University College of Physicians and Surgeons, New York, NY and 3 3DQ Lab, Stanford University, Stanford, CA The purpose of this study was to (i) evaluate the clinical and radiological outcomes of venolymphatic (VLM) and lymphatic malformations (LM) in children treated with systemic sirolimus; (ii) explore the benefit of sirolimus as an adjuvant therapy. Retrospective chart review was performed on 6 children treated with sirolimus for VLM or LM in our institution for the past three years. Volumetric analysis using 3D reconstructive software was completed using preand post-treatment MRI data. All 6 subjects were refractory to previous surgical and medical therapies prior to systemic sirolimus treatment. The subjects’ ages range from 3 to 16. Median duration of treatment was 16 (7-35) months. All six patients had notable clinical response evident by reduced swelling or pain. Average weight-adjusted post-treatment change in volume was -12.8%, with a cumulative decrease of 281.5 cm. The most significant change was a decrease of 57.9%. All patients had a greater than 10% decrease in volume. There is no clear correlation between duration of treatment and extent or response to sirolimus (p1⁄40.9). Sirolimus was well-tolerated by all patients with no significant adverse events; minor side effects included abdominal pain and vomiting at treatment initiation in one patient, and oral ulceration in one other. All six patients are still on treatment. All patients experienced clinical improvement and volume reduction in 3D reconstruction. This study concludes that sirolimus can be beneficial for both the symptomatic and volumetric improvement of VLMs and LMs, especially in children. Further molecular and genetic characterization of these patients may improve our understanding in the management of vascular anomalies using mTOR inhibitors.