Efficacy and safety profile of vismodegib in a real-world setting cohort of patients with advanced basal cell carcinoma in Argentina.

INTRODUCTION AND OBJECTIVES: Vismodegib (Erivedge® ), a hedgehog pathway inhibitor, is approved to treat metastatic or locally advanced basal cell carcinoma (BCC) not suitable for surgery or radiotherapy. Our main objectives were to study the objective response rate (ORR) assessed by treating physicians and safety of vismodegib in a real-world practice setting in Argentina. MATERIAL AND METHODS: This is a prospective cohort study in real-world practice. We included consecutive adult patients treated in Argentina with locally advanced or metastatic BCC not suitable for surgery or radiotherapy. Patients were followed until the end of the study, death, or loss to follow-up, whichever occurred first. Patients received 150 mg vismodegib PO daily. RESULT: We included in the analysis 63 patients who received treatment. Locally advanced BCC was present in 57 (90.4%) and metastatic disease in two (3.2%). ORR was observed in 46 patients (73%; 95% CI: 60.3-83.4), with partial response in 36 (57%; 95% CI: 44-69.5) and complete response in 10 (16%; 95% CI: 7.8-27.2). As to safety, 48 (76.2%) patients had at least one adverse event (AE). The most frequently observed AEs were muscular spasms in 25 (39.6%); dysgeusia in 23 (36.5%); alopecia in nine (14.2%); weight loss in seven (11.1%); and ageusia in (9.5%) patients. Serious AEs were observed in 11 (17%) patients with one episode of deep vein thrombosis and pulmonary embolism resulting in death. CONCLUSION: Our study provides additional evidence of the efficacy and tolerability of vismodegib in patients with locally advanced or metastatic BCC in a real-world practice.

Neoadjuvant Vismodegib and Mohs Micrographic Surgery for Locally Advanced Periocular Basal Cell Carcinoma.

INTRODUCTION: Vismodegib has shown a significant response rate in locally advanced periocular basal cell carcinoma. Long-term monotherapy is very difficult to accomplish due to primary or secondary resistance and side effects that limit the length of treatment. The use of Vismodegib as neoadjuvant followed by Mohs micrographic surgery is an option. PURPOSE: To report the use of neoadjuvant Vismodegib as an option for operable locally advanced basal cell carcinoma followed by Mohs surgery. PATIENTS AND METHODS: The authors treated 8 locally advanced periocular basal cell carcinomas. Mean age was 76, and 6 of 8 were women. Mean size was 18 mm (12-30). Three were recurrent after surgery. Maximal clinical response was obtained at 4.8 months. Patients were operated at the mean time of 7.3 months. RESULTS: Seven patients (87.5%) had a complete response and 1 (12.5%) progressed. Mohs micrographic surgery allowed to confirm a complete histologic response in 5 of 6 (83.3%) cases, and 1 patient refused surgery. All 7 patients are disease free after a mean follow-up of 12.4 months. All patients experienced adverse events. The most common included dysgeusia (100%) and muscle spasms (100%). Weight loss was present in 75% of the patients with a mean loss of 12.6 pounds and hair loss was seen in 50%. Only 1 (12.5%) patient withdraw from treatment because of intolerable muscle spasms. CONCLUSIONS: The authors believe there is a clear role for Vismodegib as neoadjuvant in locally advanced periocular basal cell carcinoma, even in operable cases. Specific indications beyond those already approved should be further discussed. Prospective studies to assess the combination of neoadjuvant Vismodegib followed by Mohs micrographic surgery in locally advanced periocular basal cell carcinoma with long-term follow-up are needed.

Cutaneous human papillomavirus genotypes in different kinds of skin lesions in Argentina.

Cutaneous human papillomaviruses (HPVs) comprise a large and highly heterogeneous virus group. Some of the cutaneous HPVs of the genus Beta have been suggested as a co-factor in the development of non-melanoma skin cancer (NMSC). The aim of this study was to determine cutaneous HPV prevalence and type-specific distribution in different kinds of skin lesions from Argentine patients visiting Dermatology Departments of three hospitals from Buenos Aires. A cross-sectional analysis was performed. HPV DNA was analyzed in (i) 3 patients with Epidermodysplasia verruciformis (EV) harboring benign lesions (BL) (n = 1) and squamous cell carcinoma (SCC) (n = 4); (ii) 240 non-EV patients harboring: (a) BL (n = 38), (b) Actinic Keratosis (AK) (n = 83), (c) SCC (n = 74), and (d) basal cell carcinoma (BCC) (n = 96). Detection and genotyping of 35 cutaneous HPV DNA was carried out by BGC-PCR and GP5+/6 + PCR followed by reverse line blot assay. In EV patients, Beta types were found in all lesions (5/5), including the potentially high-risk HPV types 5 and 8, mostly in multiple infections. In non-EV patients, cutaneous types were found in 50.0% of BL, 43.4% of AK, 31.1% of SCC, and 16.7% of BCC. Beta HPVs were the most frequently found in all lesions, being present in all AK and SCC cases that were positive for HPV. No type-specific correlation with lesion severity was found. In our series, a wide spectrum of cutaneous HPV types was detected in different skin lesions. A possible role for these HPVs in skin carcinogenesis deserves further study. J. Med. Virol. 89:352-357, 2017. © 2016 Wiley Periodicals, Inc.

Expression of CD44s and CD44 splice variants in human melanoma.

The ability of tumor cells to adhere and detach from extracellular matrix and endothelial cells, is a crucial step in the metastatic process and may alter the clinical prognosis of some human tumors such as melanomas. CD44, the major cell surface receptor for hyaluronate, has been implicated in cell adhesion and in tumor progression. We studied the expression of standard CD44 molecule (CD44s) and its variants v3 and v6 in 57 human primary melanoma biopsies, without previous treatment. We analyzed the association between CD44 expression and the principal clinicopathological features, including survival. Fifty-six of 57 tumors expressed CD44s, associated to the cytoplasmic membrane. No expression of CD44v3 or CD44v6 was detected. No association between CD44s expression and prognostic factors such as tumor thickness, growth type, stage or anatomic site of the lesion was found. However, a positive correlation between CD44s expression and Clark level (Spearman, p<0.001) was found. While only 33.3% of melanomas Clark I + II showed high expression of CD44s (more than 50% of positive cells), 82.6% of melanomas Clark IV + V did so. Kaplan-Meier analysis revelead that patients whose melanomas had high expression of CD44s showed a reduced relapse free survival (RFS) rate, though without statistical significance. No difference between the level of CD44 expression and overall survival (OS) was found. We conclude that melanomas only expressed CD44s, and that its level was associated with Clark's stage. CD44s seems not to be useful as a tumor marker, because it does not predict either RFS or OS.